Stem Cell Research - GSCN · tive stem cell-based strategies in regenerative medicine are in...

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Stem Cell Researchin GermanyAnnual magazine of the GSCN

zur deutschen Version p hier klicken!2013/14

re-programmingISSN (Print) 2198-7831

ISSN (Online) 2198-784X

http://www.gscn.org/Portals/0/Dokumente/AnnualReport/GSCNReport2013_DE_web.pdf

IMPRINT

German Stem Cell Network e.V.Annual Magazine 2013/14© 2014 GSCN

PublisherGerman Stem Cell Networkc/o Max Delbrück Center for Molecular MedicineRobert-Rössle-Str. 1013125 Berlin, Germany

Tel.: +49 30 9406 24-87/-88Fax: +49 30 9406 2486E-Mail: [email protected] URL: www.gscn.org

EditorsDr. Daniel Besser and Ulrike Papra (Central office GSCN) Dr. Philipp Graf (BIOCOM AG)

TranslationTom FinnisJacqui Birnie

Design & LayoutUnicom Werbeagentur GmbH, Stephen Ruebsam

PrintBuch- und Offsetdruckerei H. Heenemann, BerlinCirculation: 800

CopyrightThe magazine is part of the public relations work of the GSCN and funded by the German Federal Ministry of Education and Research (BMBF). It is supplied for a protective fee of 2€ (inclusive postage) and must not be resold. Reprint only with permission by the editors.

ISSN (Print) 2198-7831ISSN (Online) 2198-784X

FUNDED BY THE

Annual GSCN Magazine 2013/14 3

WELCOME NOTE | THOMAS RACHEL

Welcome note

Stem cell re-search counts among the most

dynamic of all the fields in the life sci-ences. Not only does the work that is car-ried out in this area open up fundamen-tal insights into the development and regeneration of cells,

tissues and organs, but also it is strongly associated with the hope for new treatment strategies. This applies in particular to the broad range of age-associated diseases that are becoming increasingly widespread in industria-lized nations as a consequence of demographic change. Regenerative medicine carries the potential for signifi-cant innovation in the development of new diagnostic and therapeutic procedures. Moreover, the findings of stem cell biology are providing a substantial impetus to the approaches of individualized medicine.

Today, in the light of this rapid progress and the complex challenges that arise during all its stages, the ongoing close cooperation of stem cell researchers has become more important than ever. This is why the Federal Min-istry of Education and Research is giving its support to the establishment of a national focal point of contact that is aimed at strengthening the international presence of German stem cell research on a sustained and long-term basis.

The German Stem Cell Network (GSCN) was officially founded on May 7, 2013. This platform will consolidate the capacities and know-how in research and indus-try more strongly than has been hitherto possible. This is reflected, for example, in the scientific and strategic working groups, which have been established to pool ex-pertise and to work towards a strong and jointly created platform for up-and-coming researchers. The German Stem Cell Network is well on the path to establishing it-self as the central voice of the research community – with international reach.

This magazine will report not only on the activities un-dertaken in the GSCN’s successful inaugural year but will also provide an overview of the issues being tackled by German stem cell researchers and the locations where these efforts are taking place. I am delighted with the commitment to a Germany-wide network of stem cell researchers that has been shown by all the stakehold-ers from science and industry, and I am confident that in their work together, they will ensure that the GSCN emerges as an active and enduring facility for the field as a whole.

Thomas Rachel MdBParliamentary State Secretary to the Federal Minister of Education and Research

4 Stem Cell Research in Germany

PREFACE | ANDREAS TRUMPP

investigators. The first annual conference in Berlin was attended by almost 400 participants from academia and industry, who made full use of the opportunity to exchange views on the latest results, methods and prac-tices across all areas of stem cell research. Preparations are now in full swing for the second annual conference at the German Cancer Research Center in Heidelberg on November, 3 - 5, with the anticipation being high that this meeting will build on the success of the inaugural conference.

Here we provide you with an outline of some of the rel-evant activities in the various sub-domains of German stem cell research. Prominent German scientists lead and coordinate each of the GSCN scientific working groups. These working groups cover the research are-as of pluripotency and reprogramming, developmental biology, adult stem cells, stem cells in diseases (cancer stem cells) and regenerative therapies, stem cells in disease modelling, and the quantitative study of stem cell biology via the application of mathematical model-ling and systems biology. As it becomes evident already from these topics alone, stem cells play a role in embry-onic development, in the formation, preservation and re-pair of adult organs and tissues, as well as in the normal aging process. Impaired stem cell activity can result in degenerative diseases or cancer. In the field of medicine, cellular model systems based on reprogrammed patient cells can aid the testing and development of drug candi-dates. Blood stem cells have been successfully applied for decades in bone marrow transplantation, while innova-

Hardly a month passes with-out a major

news story from the rapidly growing field of stem cell research: new reprogramming techniques, targeted strategies for com-bating cancer stem cells, and the novel use of stem cells in

regenerative medicine, to name but a few. In recent years, Germany’s stem cell researchers have become world leaders in this field. Now, thanks to the generous support of the Federal Ministry of Education and Research (BMBF), the German Stem Cell Network e.V. (GSCN) has been founded with the aim of bringing all German stem cell researchers together under one umbrella. This new body will strengthen German stem cell research at an international level and provide a viable structure for future challenges through serving as a single contact point for global activities and cooperations at a Euro-pean and international level. Research inter actions will be enabled between scientists, physicians and industrial partners within Germany to better explore and bolster the increasingly complex areas of stem cell research and regenerative medicine.

In addition, the network will be responsible for tasks relating to public relations and the promotion of young

Preface


PREFACE | ANDREAS TRUMPP

tive stem cell-based strategies in regenerative medicine are in development worldwide or have already been suc-cessfully introduced, such as the technique of adult stem cell transplantation for corneal replacement.

This magazine also represents the first annual report of the GSCN. We are very proud of what has already been achieved, and also on behalf of founding president Oli-ver Brüstle, we would like to thank the GSCN central of-fice for their extraordinary commitment, as well as the numerous members who have helped in shaping the Stem Cell Network over the past few months. We aspire to bring many more stem cell researchers on board as members of the GSCN, and look forward to their contribution towards the ongo-ing and dynamic development of the network.

We trust that you will en-joy reading the first is-sue of the GSCN annual magazine! In these pages, you will discov-er not only the Ger-

man stem cell research landscape but also the accompa-nied research institutes and companies that are already members of our fledging network.

Best regards,

Andreas TrumppActing GSCN PresidentHead of the Division for Stem Cells and Cancer at the

DKFZ and Director of HI-STEM, Heidelberg

Oligodendrocytes and precursor cells from pluripotent stem cells

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INDEX

Working group: Pluripotency and re-programming 18

Flexible cell programs under the spotlight

Working group: Somatic stem cells and development 22

The sources of regeneration

Welcome note Thomas Rachel (BMBF) .........................................3

Preface Andreas Trumpp, Acting GSCN president ......5

Interview with the GSCN Founding President Oliver Brüstle .................................8

The GSCN central office in profile ...............................................10

The GSCN Annual Conferences ....................................................11

The GSCN Annual Conference 2014 .................................17

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Working group: Stem cells in regenerative therapies 30

The basis of regenerative medicine

Working group: Stem cells in disease modeling & drug development 34

Personalized medicine in the Petri dish

Working group: Computational stem cell biology 38

Lending predictability to stem cells

GSCN Annual Report 2013 ............................ 42

26

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INDEX

Working group: Stem cells in diseases (cancer stem cells) 26

Targeting the seedsof tumors

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GSCN | INTERVIEW OLIVER BRÜSTLE

In a conversation with GSCN’s annual magazine, Prof. Oliver Brüstle talks about building a network for stem cell research in Germany, the latest research results and the need for ongoing development, in particular in Germany.

GSCN annual magazine: Professor Brüstle, you have played a leading role in the development of the GSCN over the past year. Did you manage to fit anything else into 2013?Brüstle: We worked in a team – it would not have been possible without the staff from the central office and other colleagues on the executive board. We also bene-fited from our experiences in establishing the Stem Cell Network North Rhine Westphalia.

You’ve been involved for some time in an initiative for a German network for stem cell research. Can you give us some background on its history?In fact we’ve been working on this idea for many years. The first discussions with the Federal Ministry of Educa-tion and Research were back in 2005. During that period we already had an extremely well functioning network for stem cell research in North Rhine-Westphalia as well as the idea that this could be a good template for a net-work at a national level.

The German stem cell network comes at a very late time point. Many national and international net-works were founded up to ten years ago, and some have already ceased their activities. So why at this moment in time do we need a German stem cell net-work?It was a different situation ten years ago. Back then, it was all about getting the field established. Everything was new, there was a strong need to identify and integrate the re-searchers in and around this area. Many locations around the world have recognized this need and es-tablished successful networks and structures. For some of them, this was already ‘mission accomplished’. We think this is somewhat shortsighted.

So what can a ‘network 2.0’ accomplish today?The need for a network is greater than it’s ever been. This is firstly due to the fact that the field has developed enormously. It’s no longer only about embryonic versus adult stem cells. With cell reprogramming and direct transcription factor-driven cell conversion, completely new technologies have come into play that open up fas-cinating biomedical perspectives. Secondly, the field has now reached maturity in numerous application areas. Regulatory issues and clinical studies pose new challeng-es. Added to this is the dark side of unproven therapies.

second generation”Interview with GSCN founding president Oliver Brüstle

These are important questions that have to be discussed in a network and communicated to the public. Further-more, the now well-established field of stem cell research and its representatives have their own very special re-

quirements, ranging from lobby-ing for specific funding programs via mentoring in career planning all the way up to professional out-reach activities. This amounts to a

great many tasks, which is why we believe that now the time is just right to create a second-generation network.

How did you determine the requirements for the GSCN?Firstly, we went to the community, meaning that we ap-proached potential members and also carried out an on-line survey. We got great feedback from this, which moti-vated us enormously and helped us to define the goals and activities of the network.

The GSCN has established a number of working groups. What will be their functions and goals?From the very beginning, I wanted more than just a net-work with an annual conference and a website. To as great an extent as possible, the members should be in-

Oliver Brüstle at the GSCN Annual Conference 2013

“The time is just right to create a second-generation network.“

“A network of the

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GSCN | INTERVIEW OLIVER BRÜSTLE

volved in the substantive work as well as be granted the corresponding external visibility. The idea is for these to be accommodated by the working groups. Scientists in all career stages are engaged in these groups, shaping con-tent and structures of the network. This is a bottom-up ap-proach, as opposed to traditional hierarchical structures where many people working in secret with only the board being visible to the outside.

How are the working groups configured?There are two categories. The scientific working groups focus on specific fields of stem cell research, such as certain classes of stem cells and specific applications. Then there are the so-called strate-gic working groups, which work on strategic issues that are relevant to scientists and socie-ty. Examples are career development, funding programs, regulatory issues, and information on available stem cell therapies. From the patients’ perspective there is a huge need for information on what are serious versus unprov-en therapies. Rapid communication of emerging stem cell technologies to both scientists and the public, too, is an important strategic area of activity.

Stem cell research is considered a technology of the future. What answer would you give to critics com-plaining that stem cell research has fallen short of expectations?Therapy development is laborious and demands the greatest possible care. In conventional pharmaceutical research, you expect development work to take at least 10 years un-til a marketable drug is produced. Just over ten years after the intro-duction of embryonic stem cells, we are witnessing first clinical studies, for example for the treatment of retinal diseases. Furthermore, stem cells are increasingly employed in the context of drug development, where they provide unique opportunities to test and vali-date compounds at a very early stage of the pharma value chain, thereby avoiding costly late failures. Looking at all this, there is no need for doomsday mongering at all.

Your own research at the Institute for Reconstructive Neurobiology at Bonn University and at LIFE&BRAIN GmbH focuses on neural stem cells derived from pluri-potent stem cells. What can these cells be used for?We are following two directions. Firstly, we are using these cells to establish cell culture models of neuro logical diseas-es, which we exploit for elucidating disease mecha nisms and as tools for drug development. This is particularly in-teresting for neurons derived from reprogrammed patient cells. Using the iPS cell technology it has become possible to identify and validate pharmaceutical compounds in patient-specific and disease-relevant human cells. On the

other hand we are developing stem cell-based therapies, for example for cell replacement in diseases such as Par-kinson’s or for stem cell-mediated gene therapies for the treatment of metabolic diseases.

What do you think is the most exciting development in this area?For me that’s the recent advances in direct cell fate conver-sion – the possibility to convert a somatic cell type straight into another one – without reprogramming the cell to pluripotency. If this works in the living organism, we could

think about directly inducing new neurons in the brain – without resorting to cell transplantation anymore.

In an international comparison, what is the current position of German stem cell research? What are our strengths?As a consequence of the legal situation, we are further ahead in the area of adult stem cells and cell reprogram-ming than in the use of embryonic stem cells, for which clinical trials have already been conducted in other places. Overall, we are on a par with the other European coun-tries, the US and Asia. For further development of this field it is important that we set up suitable funding programs to ensure that results evolving from basic stem cell research are converted into applications.

What advice would you give to young researchers? To follow their own interests and their own enthusiasm,

and to not pay too much attention to predictions and alleged career opportunities. The field is chang-ing too quickly to be able to plan ahead over a matter of years. You

live from your enthusiasm, which is the energy that makes everything possible.

Prof. Dr. Oliver Brüstle, born in 1962, is director of the Institute for Reconstructive Neurobiology at Bonn University and co-founder and CEO of LIFE&BRAIN GmbH, which serves as commercial hub of the University of Bonn Medical Faculty. His scientific focus is the use of pluripotent stem cells for research into and treatment of neurological disorders. In his role as founding president of the GSCN, he can capitalize on his ten years of experience on the board of the extraordinarily successful Stem Cell Network North Rhine Westphalia. During his presidency, the GSCN was able to position itself as a fresh force in the research landscape as well as establish the struc-tures that now serve as the basis for the future orientation of the GSCN.

“Scientists in all career stages are engaged in these groups, shaping

content and structures of the network.”

“Therapy development is laborious and demands the greatest possible care.”

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GSCN | CENTRAL OFFICE

The GSCN central

The central office of the German Stem Cell Network e.V. (GSCN) is currently based at the Max Del-brück Center for Molecular Medicine (MDC) in

Berlin-Buch. Thanks to the support of the MDC, it was possible from 2012 to undertake important prepara tory work, leading up to the first phase of start-up funding from the Federal Ministry of Education and Research (BMBF) in March 2013.

The central office is where the threads of the network’s various activities converge. The employees work closely with the executive and the extended board of the GSCN. It is here that the requests and concerns of the GSCN mem-bers and the working groups are addressed and imple-mented within the program’s framework of possibilities. Among other duties, the GSCN central office takes care of membership administration and is responsible for organizing the general assembly and the international annual conference. The office is also tasked with pre-paring the working group- and committee meetings and organizing thematic symposia and workshops. Within the scope of these events, the GSCN central office and the network panels aim to jointly identify needs for action and convert these into concrete activities. The events are also important for recruiting new members.

Other responsibilities for the central office include the compilation of the GSCN annual magazine – the very first issue is in your hands – and the production of other in-formational materials. The office also attends to the de-velopment and construction of the GSCN website, the on-line communication platform, and a database of experts. The central office operates in cooperation with national and international partners in order to implement the objectives of the GSCN. In particular, collaboration with international organizations is of central importance for the future development of this exciting field of research. Today, stem cell researchers have new opportunities to network globally with one another, and the GSCN will be a key part of this process. To this end, the GSCN central

office will encourage and facilitate the expansion of international

research consortia, and co-operation efforts between education, research and industry.

Future plans at the GSCN include public events, press events and par-liamentary evenings on stem cell research. These events will be coordi nated

and logistically prepared in consultation with the corres pon-

ding working groups. The intention here is to establish a central platform on the topic of stem cell research – for the researchers themselves (information on funding programs), the general public (information for patients and schools), the press (position statements on current events), and politics (policy recommendations). In order to establish greater proximity to the general public and policy makers, the central office of the GSCN will move to Berlin’s city center in late 2015. To further expand GSCN public relations efforts, the central office team will as of this year be reinforced by a person for communication.

Central office, German Stem Cell Network (GSCN) e.V.c/o Max Delbrück Center for Molecular Medicine (MDC) Berlin-BuchRobert-Rössle-Str. 1013125 Berlin, GermanyTel: +49 30 9406 24-88/-87Fax: +49 30 9406 – 24-86Email: [email protected] [email protected]

As Managing Director, Dr. Daniel Besser is responsible for the manage-ment of the central office of the German Stem Cell Network. Already in the initial phases, the biologist accompanied the founding and development of the network in the role of coordinator. Besser can also look back on 20 years of recognized expertise in the field of molecular biology. His work on stem cell research began in 2002 as a scientist in the group of Ali Brivanlou at Rockefeller University in New York. From 2004 to 2011, he headed a research group at the MDC on the topic of stem cells. In this capacity, he has actively participated in a variety of events and organized conferences on the subject of stem cells.

Ulrike Papra has supported the GSCN central office since June 2013 in the

role of assistant. She completed her studies on International Information Management at the University of Hildesheim, with a focus on Informa-

tion- and Communication Sciences, Business Studies and Media Studies. Her

seven years of experience as a senior project coordinator at the event- and communications agency MCI Group has provided her with proven expertise in the planning and implementation of national and international conferences in the areas of medicine and science.

office in profile


GSCN | ANNUAL CONFERENCES

The

GSCNAnnual Conferences

Concept and Facts

The Annual Conference is the GSCN’s key event. It is held in different locations in Germany. The intention at the GSCN annual conferences is to

draw attention to the national networking of scientists, rather than solely focussing on inviting well-known in-ternational scientists. Contributions from lectures and poster presentations are sorted into topic areas to pro-vide a platform for the broad field of basic and applica-tion-oriented stem cell research with its associated areas of regenerative medicine and drug research as well as to stimulate fruitful discussions, interactions and col-laborations. Most of the lectures are selected from the submitted abstracts in order to offer a forum for young

scientists, from PhD students to junior team leaders. The GSCN’s scientific working groups determine the content of the many individual sessions at the annual conferen-ces. In addition, relevant general topics, such as outreach programs, career development and appropriate funding measures, are covered in sessions hosted by the strategic working groups. Selected international keynote speakers create the framework for the conference. The annual conference is also a forum for companies, who are given the opportunity to showcase themselves in an industry session and at an exhibition. Workshops for the further qualification of young scientists, for example, and events for interested members of the public are planned for future conferences. p

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1st Annual Conference of the GSCNThe first Annual Conference of the GSCN was held in the Max Delbrück Center for Molecular Medicine (MDC) in Berlin from November 11 – 13, 2013. With 400 partici-pants from home and abroad, 21 exhibitors and 240 abstracts submitted, the conference was a resounding success. All the important stem cell research groups from Germany were represented. Without exception, extreme-ly positive feedback on the event was received from the participants, GSCN members, speakers and chairs as well as the companies taking part.

Scientific Lectures

At the opening event, Walter Rosenthal, director of the MDC, welcomed the participants to the Max Delbrück Communications Center. Oliver Brüstle (Bonn), found-ing president of the GSCN, explained why a stem cell network in Germany had come at exactly the right time and described the GSCN’s vision to the plenum. The con-ference’s scientific program started with a lecture by re-nowned stem cell researcher Michele de Luca (Modena, Italy). He presented the huge successes of using epithe-lial stem cells in the clinical setting for skin transplants and for injuries to the cornea of the eye. He stressed that

excellent basic research is the principal requirement for innovative stem cell therapies. In the following lecture, Vania Broccoli (Milan, Italy) went into results from his laboratory regarding the direct reprogramming of so-matic cells to neuronal cells, in particular induced dopa-mineric (iPA) neurons, and their functional properties. These cell types are crucially important to understanding Parkinson’s disease and possible future cell therapies.

Opening of the 1st GSCN Annual Conference

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During the three days of the conference, the program included 27 presentations on a large number of topics:

• Pluripotency and embryonic stem cells• Cancer stem cells in solid tumors• Stem cells in tissues of meso- and endodermal origin• Stem cells in regenerative therapies• Programming und reprogramming• Stem cells in tissues of neural and non-neuronal

ectoderm• Stem cells in disease modeling and drug development• Stem cells in development• HSCs and stem cells in hematopoietic malignancies

The conference proceedings, which are available on re-quest from the GSCN office, contain condensed summa-ries of the presentations. In group discussions at the end

of the sessions, the goals of the respective GSCN working group were debated

and further measures planned. These discussions gave the

members of the individual working groups the oppor-tunity to codetermine their future content.

The scientific program was brought to a close on Novem-

ber 13 with two high-calib-er keynote lectures. Christine

Mummery (Leiden, Netherlands) presented a large number of

applications for heart muscle cells that can be created from pluripotent stem cells. These cells are now used in her lab-oratory and others for safety tests on drugs, for discovering

novel compounds and for stud-ies on diseases. In the EMBO Key-

note Lecture, Austin Smith (Cam-bridge, UK) concluded the conference

by examining the “Design principles of pluripotency”, i.e.

the central transcription factors and signaling molecules which maintain the pluripotent state in embryonic stem cells. He particularly detailed the relationship between the naïve and the primed state in pluripotent cells of the mouse and drew comparisons with cells of the germ line. Recently published data on the naïve state in the human system came under the spotlight in the discussion that followed.

The first annual conference closed on Wednesday after-noon with the change at the helm from the founding pres-ident Oliver Brüstle to the new acting president Andreas Trumpp. Trumpp ended the conference in Berlin with an overview of the GSCN’s plans for 2014 as well as an in-vitation to the second annual conference in Heidelberg.

Poster Exhibition

With a total of 193 poster presentations, the poster sessions on the first and second day of the conference offered extensive insights into the current status of stem cell research. They were very well-attended by the participants. The scientists had enough time on both evenings to discuss the data from the various laborato-ries and the latest developments in the field with their colleagues. Many participants on site stated that they were very pleased to be present at the first annual con-ference and had already made new contacts. Prizes for the best posters were provided by GSCN member com-pany Peprotech GmbH and – for a contribution from applied stem cell research – by GSCN member institute Fraunhofer IZI in Leipzig.

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GSCN | JAHRESKONFERENZEN

The poster prizes went to:− Mehdi Pirouz (Göttingen): Mad2l2-deficient mouse

embryonic stem cells are unstable and deviate into primitive endoderm

− Miha Modic (Cambridge/Munich): Regulation of alter-native polyadenylation by hnRNPs in human embryonic stem cells

− Liang Fang (Berlin): Novel small-molecule antagonists of β-catenin/TCF4 interaction: interference with the self-renewal of cancer stem cells

− Robert Fordham (Cambridge): Transplantation of expanded foetal intestinal progenitors contributes to colon regeneration after injury

Poster prize for applied stem cell research:− Bella Rossbach (Berlin): Human induced pluripotent

stem cells for cell-replacement therapy: Exploring their immunogenicity and immunomodulatory properties

The GSCN would also like to congratulate the recipients of the GSCN Travel Awards: Bianca Buechner (Hannover), André Görgens (Essen), Leonid Schneider (Darmstadt) and Edda Schulz (Paris, France).

Strategic Working Groups

In the session of the strategic working group “Career Development”, Thorsten Abs (Ham-burg) from academics.de, an online job market for science, research and development, spoke about var-ious professional opportuni-ties for life scientists. He also talked about the require-ments and demands for young scientists to work in alternative scientif-ic fields. In the session of the working group “Funding Programs and Policies”, Jürgen Sautter (Brussels, Belgium) from the European Commis-sion explained strategies of research funding at EU level within the new research frame-work program Horizon 2020. He summarized the current political re-lationships, the financial framework from

2014 to 2020 and the priorities of Horizon 2020. Within the course of this program, there will be good financial funding for biomedical questions including regenerative medicine and stem cell research. The huge importance of communication in stem cell research was emphasized in the session “Outreach activities and public percep-tion of stem cell thera pies” by Emma Kemp (Edinburgh, Scotland). She presented materials for providing infor-mation about stem cell research that had been created by the EuroStemCell consortium for the wider public and as teaching mate rials for schools. Gisela Badura-Lotter (Ulm) took a look at ethical questions of stem cell re-search, such as the moral status of the embryo. She called

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for less ambiguity in the arguments and said that all positions and opinion leaders should be taken into account. Andreas Bosio (Ber-gisch Gladbach) and Frank Em-mrich (Leipzig) presented new “Stem cell technologies” in the session with the same heading. In the session of the working group “Clinical trials and regulatory af-fairs”, Christine Günther, CEO of Mu-nich-based company Apceth, spoke about the challenges and regulatory requirements involved in implementing cell therapies in clinical practice based on the example of a clinical study recently launched by her company.

Companies Present

In the industry session, GSCN member companies AMS Biotechnology, Eppendorf, Essen BioScience, Life Tech-nologies and Peprotech with the addition of Apceth, BD Biosciences, Fluidigm and Nanostring introduced the latest technologies and methods for stem cell research. There was a very positive response to the industry ses-sion and the industry exhibition. In an online evaluation after the conference, the participants rated the orga-nization of the conference as excellent (4.64 points out of 5) and the number and length of the breaks as well as the opportunities to interact with other participants as outstanding (3.82 points out of 5). Roland Leathers

from the GSCN member company Life Technol-

ogies stressed, “It is very important that German scientists come together here to discuss all the aspects that are rel-evant for stem cell research.” Nicolas

Danzenbächer from Peprotech, also a GSCN

member company, refer-ring to the motivation of

their companies within the framework of the GSCN, said,

“We are always happy to take part in any efforts to unite the German stem

cell field.”

Networking in the Evenings

The networking evening to which all conference participants were in-vited took place on Monday at the “Alte Pumpe” in Ber-lin’s Tiergarten district. Berlin’s historic monu-ment from the year 1883 with its Ph

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meticulously restored industrial side provided a unique ambience for getting to know people and exchanging ide-as and opinions on scientific work. As one of the partici-pants said, “This is how science works – we can’t just do it on our own.” And another scientist said, “Once you’ve had a beer with them (collaborating scientists), it makes things much easier.” The networking evening was also given a very positive rating (4.21 points out of 5) by con-ference participants in an online evaluation. On Tuesday evening, the get-together after the Annual General Meet-ing of the GSCN offered even more opportunities to ex-change views and opinions.

Results of the online evaluation

The online evaluation showed a good overall response to the con-ference. The participating in the survey gave the variety of top-ics, opportunities for interac-tion and the conference in general a excellent average rating of 3.88 points out of 5. The conference concept itself, with a large number of presentations that were selected based on the sub-mitted abstracts as well as several international key-note speakers, achieved an impressive 4.09 points out of 5. The organization of the group discussions in the work-ing groups was deemed to require optimization at the next annual con-ference (3.41 points out of 5). Almost

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3/4 of those participating in the survey said that they would like to attend the next conference of the GSCN. The GSCN and its working groups are greatly looking forward to the next GSCN annual conference which will take place in Heidelberg from November 3 – 5, 2014 (see page 17).


GSCN JAHRESKONFERENZ

International keynote speakers

Scientific sessions

• Pluripotency and embryonic stem cells• Programing and reprograming• Stem cells in development• Stem cells in tissues of neural and non-neuronal ectoderm• Stem cells in tissues of mesodermal and endodermal origin• HSCs and stem cells in hematopoietic malignancies• Cancer stem cells in solid tumors• Stem cells in regenerative therapies• Stem cells in disease modeling and drug development

Strategic topics

• Funding programs• Clinical trials and regulatory affairs• Career development• Public outreach• Public discourse on therapies• Emerging technologies

Session chairsGisela Badura-Lotter · Andreas Bosio · Thomas Brabletz · Thomas Braun · Oliver Brüstle · Tobias Cantz · Michael Cross · Micha Drukker · Frank Emmrich · Georg Fuellen · Hartmut Geiger · Ira Herrmann · Andreas Kurtz · Karl-Ludwig Laugwitz · Ulrich Martin · Albrecht Müller · Ingo Roeder · Hans Schöler · Insa Schröder · Elly Tanaka · Mathias Treier · Torsten Tonn · Andreas Trumpp · Hans-Dieter Volk · and others

Program committeeDaniel Besser (Berlin) · Thomas Braun (Bad Nauheim) · Oliver Brüstle (Bonn) · Micha Drukker (München) · Ulrich Martin (Hannover) · Ana Martin-Villalba (Heidelberg) · Elly Tanaka (Dresden) · Andreas Trumpp (Heidelberg)

Abstract submission deadline: July 31, 2014The 2nd international Annual Conference of the GSCN will be held from November 3 - 5, 2014 at the Communications Center of the German Cancer Research Center (DKFZ) in Heidelberg. The conference will cover the latest findings in stem cell biology in Germany and beside selected international keynote lectures many scientists will get the chance to present their work to a wide forum.

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of the German Stem Cell Network (GSCN)

November 3-5, 2014German Cancer Research Center (DKFZ)Heidelberg

www.gscn.org

2nd International Annual Conference


GSCN FACHGRUPPEN | PLURIPOTENZ UND REPROGRAMMIERUNG

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Staining of cell structures in the kidney


RESEARCH IN GERMANY | PLURIPOTENCY AND RE-PROGRAMMING

Flexible cell programs under the spotlight



disease modeling

drug development

Somatic stem cell

The field of stem cell research is currently experiencing an unprecedented boom following a series of spectacular advances in cellular reprogramming. Researchers across Germany are unlocking the secrets behind the versatility of cells, and progressively gaining a clearer understand-ing of the phenomenon of pluripotency. A dedicated GSCN working group has been established to pool outstanding national expertise in this area. The latest molecular biological methods are helping researchers to further the technique of reprogramming and promote translation into biomedical applications.

Shinya Yamanaka first demonstrated the art of repro-gramming in mouse cells in 2006 and shortly after also in human cells – an achievement for which he

has in the meantime been awarded the Nobel Prize. Since then, new developments in the field have been appearing at almost a monthly rate. Yamanaka’s crucial contribu-tion was the celebrated quartet of transcription factors Oct4, Sox2, c-Myc and Kfl4, which are used to convert dif-ferentiated skin cells into so-called induced pluripotent stem (iPS) cells (see graphic on page 33). These exhibit very similar properties to embryonic stem (ES) cells, na-mely, they are able to differentiate into virtually all of the more than 200 cell types of the body, circumventing the ethical issues that have otherwise dominated this area of science. The technology also makes it possible to produ-ce patient-specific cells that will not be rejected by the immune system.

First-class research

Today, German stem cell laboratories are making signif-icant research contributions to the field of pluripotency and reprogramming. This is reflected by a publication analysis published at the end of 2013 by EuroStemCell and the publishing house Elsevier. In a breakdown of the number and citations of publications on the subject of iPS cells in the years 2008 to 2012, two German stem cell research strongholds were in the international top 30: the Max Planck Institute for Molecular Biomedicine in Münster and the Medical School in Hannover (MHH).Hans Schöler, Director of the Max Planck Institute for Mo-lecular Biomedicine, is one of the initiators of the GSCN working group ‘Pluripotency and re-programming’. His research team has been occupied with this and re-lated issues for many years. Among other activities, the Münster-based researchers are studying the special role of the regulator and embryonic stem cell marker Oct4 in development. They are also working towards a more tar-geted and sparing application of iPS technology. To these ends, the group headed by Holm Zaehres has established the central unit ‘Stem Cell Engineering’. The MHH is also regarded as a base for iPS cell production.

The work of Ulrich Martin from the Excellence Cluster REBIRTH, which is also based in Hannover, includes the iPS-based production of cardiomyocytes. Together with his team, he is pressing ahead with the production of large quantities of cells in specially designed bioreactors.

Driving forward iPS technology

The advances that have been made in iPS technology are breathtaking. Researchers in stem cell laborato-ries in Germany and around the world are continuous-ly refining the formulation and making iPS technology more safe and efficient. Notable is Micha Drukker group among these from the Institute for Stem Cell Research at the Helmholtz Center Munich and the second of the three initiators of the scientific GSCN working group. “Among other techniques, we use artificial mRNA mole-cules to reprogram the cells,” says Drukker. “They quickly and efficiently convert human cells into iPS cells.” This means that it is important that production is as speedy as possible, to ensure that further mutations do not ac-cumulate in the cell culture. Drukker is currently setting up a central service unit – the ‘hiPS Cell Unit’ – at the center’s Neuherberg site. On the basis of iPS cells from healthy individuals as well as patients, this will serve as an experimental platform for research partners for the production, thorough verification of iPS cells, and their differentiation into specific cell types. Similar initiatives are underway at other German locations in Berlin, Bonn, Dresden, Hamburg, Hannover, Münster, and span numer-ous departments at the Bavarian university-based loca-tions of the ForIPS research network.

Understanding complex networks

The artificial induction of pluripotency in cells is one thing, but understanding how this state is actually regulated is another thing altogether, says Drukker. “This happens through a complex interplay of gene ex pression programs, epigenetic mechanisms and signaling pro-cesses,” explains the stem cell researcher. “We want to decode the interweaving elements in this ensemble.” Drukker is interested in the specific developmental stage in the life of a pluripotent stem cell when it becomes a progenitor cell. The stem cell researchers are now looking for answers for a range of key issues, also in the context of the GSCN working group.

How is pluripotency regulated, in particular in naive cells or other cells that are more restricted in their develop-mental potential, so-called ‘primed’ ES cells? What are the differences between ES cells in mice and humans? How similar, in reality, are ES cells and iPS cells? To an-swer these and other questions, the various cell types and cell stages are being investigated more intense-

Pluripotency and re-programming


Max Delbrück Center for Molecular Medicine (MDC)

Located in Berlin-Buch, the MDC carries out high-quality, interdisciplinary research on basic mechanisms and applications in major human health threats including cancer, cardiovascular

and metabolic diseases, and disorders of the nervous sytem. These thematic research areas are supple-mented by the Berlin Institute for Medical Systems Biology (BIMSB) at the MDC and the MDC-Charité partnership in the Berlin Institute of Health (BIH).

Interesting projects for PhD students, postdocs, and group leaders are available on themes related to stem cells including hematopoiesis and immune sys-tem development, cancer surveillance, cancer stem cells, organ differentiation, etc. Professor Mathias Treier, senior group leader at the MDC, states: “Opportunities for partnerships with clinical groups,

a range of cutting-edge technology platforms, and superb animal facilities for diverse model organ-isms make the MDC an excellent site for stem cell research.”

Contact: Max Delbrück Center for Molecular Medicine, Berlin-BuchRobert-Rössle-Str. 1013125 Berlin, Germanywww.mdc-berlin.de

RESEARCH IN GERMANY | PLURIPOTENCY AND RE-PROGRAMMING

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ly than ever before. For example, in the laboratories of Martin Zenke and Wolfgang Wagner from the Institute for Biomedical Technologies at RTWH Aachen. And by James Adjaye at the Düsseldorf University Clinic, who is employing systems-biological methods, among others, to approach the phenomenon of pluripotency.

Direct programming

Another development that is the subject of consider-able attention is the so-called direct programming or trans-differentiation of one cell type to another, entirely without the intermediate pluripotent stem cell stage. Re-

searchers are now working to further simplify this direct reprogramming of cells. Also here, German researchers are making vital contributions to this emerging field of research. For example, Hans Schöler and his team have succeeded in transforming skin cells directly into neural stem cells. Frank Edenhofer at the University of Würzburg and Oliver Brüstle from the Bonn-based Institute of Reconstructive Neurobiology and LIFE&BRAIN research center are likewise occupied with the direct transformation of skin cells into induced neu-ral stem cells (iNSCs), and with refining the correspond-ing protocols.

Activating reprogramming in the body

Mathias Treier, research group leader at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin, is the third initiator of the GSCN working group. Taking the perspective of a developmental biologist, he is focused on cellular decisions in living organisms. “One shouldn’t forget that the ES cells and iPS cells generat-ed in the laboratory are artificial systems,” says Treier. For this reason, he considers laboratory-derived cell replacement in regenerative therapies very limited to a few diseases. “Rather, we need to stimulate the self- healing process locally in the organs” says Treier. Being able to identify the right switch is vital in this kind of in vivo reprogramming. Treier and his team have dis-covered a molecular switch in mice that can bring about a functional transformation of ovaries into testicular tissue. Such switching events could also happen in the brain, for example in the transformation of glial cells into neurons. This phenomenon is now being investigated by Magdalena Götz of the Institute of Stem Cell Research at the Helmholtz Center Munich and by Benedikt Berninger at the University of Mainz.

Research networks in Germany

In recent years, various approaches aimed at further ex-ploring the potential of pluripotency and cell program-ming have been provided with support by the important


www.essenbioscience.com Live Content Imaging Within Your Incubator

The CellPlayerTM Kinetic Stem Cell Application using the IncuCyte ZOOMTM Live Content Imaging System. Seven days after reprogramming fibroblasts with CytoTune®, transitioning cells are re-seeded onto feeder cells. Colony emergence over time was observed. Here, representative images taken day 7, 12 and 17 during reprogramming show a colony’s evolution.

Capturing rare events in iPSC reprogramming.

Continuous monitoring of cell growth and behaviour can greatly enhance the validity of any tissue culture process or cell based assay. iPSC laboratories continue to work towards more efficient methods of deriving cells but stem cells and somatic precursors can be fragile and inspection under the hood can be arduous. The IncuCyte high throughput microscope is uniquely placed to allow remote monitoring - without removing cells from the incubator. Simplifying and automating key elements of inspection with the IncuCyte re-duces the time spent in non-ideal conditions for both the cells and the oper-ator and provides a major key to success. Now work often done in a TC hood is done at your desktop PC, images from multiple wells and multiple flasks

are delivered, without disturbing the cells, straight to any suitably networked remote location. Software tools allow colony tracking and marking, and plate marking tools reduce the burden of relocating colonies during maintenance. With continuous monitoring unique insights to the emergence of new, rare and unforeseen events can be found.

For more information visit www.essenbioscience.com or contact Dr Peter Djali, European Sales Manager, [email protected]

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German research funding organizations. Among others, the Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) has financed the priority pro-gram SPP 1356 ‘Pluripotency and Cellular Reprogramming’, coordi nated by Albrecht Müller of the University of Würzburg. The program, which began in 2008, comprises the interdisciplinary contributions of more than 25 working groups from across Germany. Likewise, the Federal Ministry of Education and Research (BMBF) is providing targeted support for alternative methods of ob taining stem cells. Projects on cell programming represent a major part of research funding at the Stem Cell Network North Rhine Westphalia. The contribution of these and other research projects are enabling Ger-many to keep pace with the rapid advances in the field that are taking place globally. However, as result of com-paratively restrictive stem cell legislation, the required know-how for the study and use of pluripotent cells has advanced less quickly in Germany than in other coun-tries, where experimentation with human ES cell lines was permitted from very early on.

“We want the GSCN working group to further intensify scientific exchange in Germany,” says Treier. The working

group is now set to serve as a nucleus for future collabo-rations. In the context of the group, the Munich-based re-searcher Micha Drukker anticipates the development of projects such as online databases, which would be used to share protocols, among other things. The scientist is also considering workshops open to all GSCN members, in which they could pass on their knowledge of new molecular biology technologies. Text: Philipp Graf


RESEARCH IN GERMANY | SOMATIC STEM CELLS AND DEVELOPMENT

The sources of regeneration

Collaborative Research Center 873Maintenance and Differentiation of Stem Cells

The Collaborative Research Center SFB 873 “Maintenance and Differentiation of Stem Cells in Development and Disease” at Heidelberg University works towards defining the regulatory principles underlying the balance between main-tenance, expansion and differentiation of stem cells in diverse systems on a mechanistic level. To this end the SFB873 studies a wide spectrum of experimental models ranging from plants to human to elucidate the inherent properties of specific stem cell systems, but also to unco-ver common and divergent principles behind regulatory regimes and molecular signatures.

Our consortium brings together internationally recognized researchers, with unique scientific strengths in cell biology, biophysics, developmental biology, molecular medicine or modeling. With our research we hope to advance our understanding of principles underlying stem cell function and lay the foundation for translational approaches.

Centre für Organismal Studies (COS)

Im Neuenheimer Feld 230

69120 Heidelberg

www.sfb873.de

regenerative therapiesdisease

modeling

Somatic stem cells are the driving force for growth and regeneration. When there is deterioration and injury, they replenish the body with new cells. Germany has a strong tradition in developmental biology and biomedical science specialized in the study of tissue stem cells. Using model organisms, researchers explore molecular and cellular processes that provide the body with remarkable self-healing abilities. A large number of specialists in Ger-many are dedicated to improving our understanding of the complex nature of blood stem cells. The GSCN working group is aimed at ensuring that this expertise continues to grow together.

Adult stem cells represent an indispensable reser-ve for tissues and organs, making them of major interest to developmental biologists. Traditionally,

Germany has a strong tradition in this discipline; inclu-ding a Nobel prize for the pioneering work of German developmental biologists Hans Spemann and Christiane Nüsslein-Vollhard. The field is institutionally anchored in research organizations such as the Max Planck Society, the Helmholtz Association, the Leibniz Association, the Fraunhofer Society, and numerous universities. German laboratories have been a major source of our understan-ding of regeneration processes and the biology of soma-tic stem cells. This was emphasized at the first annual conference of the German Stem Cell Network (GSCN), where the majority of presentations came from scien-tists in this field of research. Another factor has been the legislative situation, which only permits work involving human embryonic stem (ES) cells to be carried out using

imported lines, leading many researchers to focus on so-matic stem cells instead.

Shedding light on fundamental mechanisms of regen-eration requires a detailed understanding of their nat-ural functions. Here, researchers have focused on nu-merous animal species with incredible regeneration abilities, namely flatworms, fruit flies, fish, amphibians and mice, all of which are common model organisms for developmental biologists working in Germany. Elly Tanaka uses the Mexican axolotl salamander, which is renowned for its ability to regrow fully functional limbs. Tanaka works at the DFG Research Center for Regener-ative Therapies Dresden (CRTD) and is one of the initia-tors of the GSCN working group ‘Somatic stem cells and development’. Tanaka and her laboratory have already uncovered some of the reasons for the axolotl’s regen-erative abilities.

Model organisms with fascinating abilities

One finding: In contrast to previous assumptions, an amputation site does not give rise to a clump of pluri-potent stem cells but a mixture of progenitor cells. They can divide despite the fact that their developmental potential is already restricted. “Both stem cell activa-tion and dedifferentiation play a role in the regrowth of limbs,” says Tanaka. How are stem cells activated in the tissue following an injury, and how are specialized cells reprogrammed to become progenitor cells? To answer these questions, Tanaka and her team are searching for

Somaticstem cells

Somatic stem cells and development


GSCN FACHGRUPPEN | GEWEBESTAMMZELLEN UND ENTWICKLUNGSBIOLOGIE




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Fraunhofer EMBTransporting living cells safely and securely

Scientists often have to exchange cell cultures with colleagues at other institutions, with their partners in industry or other clients. Frequently, the material is transported in a frozen state. Yet when freezing it – which may take several hours – this procedure could inflict irreparable damage to the cells. But even when eventually thawed, there is still the risk that the cells will die off. Then a new cell culture has to be ordered and transported again, before the researchers can begin the scheduled experiments and analyses – a good one to two weeks later. So that living cells can be transported under optimal conditions an autonomous transportation box has

been developed at the Fraunhofer Research Institution for Marine Biotechnology (EMB) in Lübeck with which living

cells can be transported under their optimal culture conditions – such as at 37 degrees (Celsius) and with a carbon dioxide (CO2) content of 5 percent, for up to 48 hours long. This novel mini-incubator (patent pending) is lightweight and no bigger than a parcel box. An internal Lithium Iron battery operates the electronically regulated heating and the CO2 supply. Integrated sensors monitor and store these parame-

ters that are variably adjustable as well. The built-in CO2 cartouche can be re-filled from the outside. As from now the engineers and researchers completed their scientific work of the prototype development and now the cell transport box is ready for serial production.

Fraunhofer Research Institution for Marine Biotechnology EMB Paul-Ehrlich-Straße 1-3, 23562 Lübeck, Germany www.emb.fraunhofer.deContact: [email protected] [email protected]

key molecules that give the starting signal for the re-generation process. The Dresden-based developmental biologists are also taking a detailed look at other mech-anisms and aim to clarify the commands that cause pro-genitor cells to form a specific cell type.

Setting sights on muscle stem cells

Basic researchers also want to understand how to in-duce, facilitate and regulate regenerative processes. The experiments are motivated by the assumption that the molecules that are responsible have close relatives in humans that might also be subject to activation. This is the goal of Thomas Braun, Director of the Max Planck Institute for Heart and Lung Research in Bad Nauheim. Braun, co-initiator of the GSCN working group, is con-centrating on satellite cells: adult stem cells in skeletal muscle tissue. “We have found important factors that regulate and activate the self-renewal of these stem cells,” says Braun. A particular focus of the Max Planck researchers is a muscle that is typically known for low regeneration abilities: the heart. Braun’s team has identified a population of stem cells in mice that can contribute to the renewal of heart muscle cells. Some evidence suggests that in stressful situations, new heart muscle cells can “rewind” their development program and thus regain the ability to divide. These ‘dedifferen-tiated’ heart muscle cells are similar in several respects to somatic stem cells. Now the Max Planck researchers have succeeded in identifying the genes required for this process. “In principle, the mammalian heart is in a position to initiate regeneration processes, although under normal circumstances it is not sufficient to cure heart damage,” says Braun. The objective now is to find means of stimulating the formation of new heart muscle cells using cardiac stem cells.

The German research landscape

Researchers in Germany are actively exploring the biology of stem cells in almost all tissue types in animals, humans, and even plants. The Deutsche Forschungs-

gemeinschaft (DFG, German Re-search Foundation) is supporting specific collaborative projects for basic research into stem cells, for example as part of the activities of the special research fields SFB 655 in Dresden and SFB 873 in Heidelberg. Fund-ing from the Fede ral Ministry of Education and Research (BMBF) is particularly aimed at applica-tion-oriented research. At the Eu-ropean level, German stem cell re-searchers are involved in consortia that are financially supported by the European Commission. The progress of these projects to date are a testament to the dynamism and exper-tise of stem cell research in Germany.The following overview highlights just a few of the core areas.

Stem cells in the blood

The blood – a rich source of somatic stem cells – is an important topic of stem cell research. A number of working groups across Germany focus on mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs). These efforts are aimed at tapping the high potential of such cells for clinical applications (see the section ‘Stem Cells in Regenerative Therapies’).

Research teams headed by Anthony Ho and Andreas Trumpp in Heidelberg and Albrecht Müller from the University of Würzburg are studying the genetic and epigenetic profiles of MSCs and exploring their unique properties for regenerative therapies. Work by Claudia Waskow from the Center for Regenerative Medicine in Dresden CRTD led to the discovery of several different forms of blood stem cells, and the role of DNA repair in HSCs is under scrutiny by Andreas Trumpp and Michael Milsom in Heidelberg. Researchers led by Gerd Klein at the University Hospital Tübingen and Cornelia Lee

Axolotl



Chair Tissue Engineering and Regenerative Medicine (TERM)Artificial Vascularized Tissues

Implants with autologous cells are engi-neered by Tissue Engineering methods which minimize the body´s own implant rejection. The hereby activated self-healing mechanisms result in tissue regeneration (Regenerative Medicine).We develop human test systems as alternative tissue models to animal trials. Tissue specific bioreactors providing culture conditions of the cell´s natural microenvironment in the body are created to ensure in vitro functionality of the used cells. A biological vascularized scaffold, the BioVaSc, is applied to generate

vascularized tissue in vitro. Tissue models as well as models for cancer or (infectious) diseases have successfully been set up.

Chair Tissue Engineering and Regenerative Medicine (TERM) Universtiy Hospital WürzburgRöntgenring 11 97070 Würzburgwww.term.ukw.de

Tissue-specific bioreactors and incubators.

Thedieck from the Karlsruhe Institute of Technology focus on mechanisms at work in the hematopoietic stem cell niche. This niche is also the subject of investigation of a dedicated DFG Research Group (FOR 2033)coordinated by researchers in Mu-nich. Cord blood also exhibits great po-tential as an alternative source of HSCs.

In a BMBF joint project, researchers at RWTH Aachen University, the University of

Würzburg and MHH Hannover are working on ways to improve the expansion of these

versatile cells in the laboratory. At the Institute for Transfusion Medicine at the University of Es-

sen, several research groups have joined together in a larger team under the direction of Peter Horn. Groups led by Hannes Klump and Bernd Giebel are focused on the molecular basis of HSCs and other stem cell popu-lations.

Regeneration in organs

Heiko Lickert and his team at the Helmholtz Center Mu-nich are studying regulators that play a key role in the formation of pancreatic β-cells. Such factors are essen-tial for the production of insulin-producing cells and thus aim to provide a basis for a future cell replacement therapy for diabetes. These regulators are likewise a priority for Francesca Spagnoli at the Max Delbrück Center for Molecular Medicine (MDC) in Berlin-Buch. She is investigating how liver cells can be repro-grammed into β-cells. The laboratories of Walter and Carmen Birchmeier at the Berlin MDC are specialized in the development biology of skin- and muscle stem cells and other topics.

Numerous neurobiologists in Germany are investigat-ing adult stem cells in the brain. In recent years, they have made vital contributions to the understanding of cellular plasticity of the brain – the ability to form new neurons in the adult organ. Magdalena Götz, at the Helmholtz Center Munich, is studying neural stem cells

in the forebrain that are known to play a role in so-called adult neurogenesis. Likewise, Ana Martin- Villalba at the Heidelberg DKFZ is occupied with neural stem cells in the brain and how they are locally reactivated after inju-ry. A research focus for Gerd Kempermann at the CRTD in Dresden is adult neurogenesis and how this is influ-enced and triggered by behavior patterns.

How stem cells age

Even stem cells age, meaning that a tissue’s ability to regenerate gradually declines over time. The phenome-non of stem cell aging is the specialized subject for a number of research groups in Germany. The team of Karl Lenhard Rudolph at the Leibniz Institute for Age Research in Jena is studying the genetic defects that cause ageing in stem cells of the hematopoietic system. A related theme is the molecular mechanisms of stem cell aging, which are thought to promote tumor de-velopment. Hartmut Geiger and his team at Universi-ty Hospital Ulm are exploring signaling pathways and molecular mechanisms that lead to aging in blood stem cells. If stem cells could be rejuvenated, it could boost the regeneration process.

Ideas for joint research projects

Research activities in the field of somatic stem cells in Germany are extremely multifaceted. The GSCN working group has been established with the objective of de-fining common interests and facilitating information exchange through improved networking opportunities. “A number of people in the working group have already come together to form a new joint research project,” says developmental biologist Thomas Braun. Although the researchers are interested primarily in fundamen-tal mechanisms of stem cell biology, their insights will clearly improve know-how in the handling of cells in the laboratory. Learning to optimize recipes for the genera-tion of specialized cell types in cell culture will provide a decisive impetus for the cell replacement therapies of tomorrow. Text: Philipp GrafPh

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A kidney cancer cell after inhibiting a protein required for proper cell division


RESEARCH IN GERMANY | STEM CELLS IN DISEASES (CANCER STEM CELLS)

Targeting



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cancer stem cells

Somatic stem cell

the seeds of tumorsIncreasingly, the concept of cancer stem cells is gaining acceptance within the medical community. Around the world, researchers regard these rare malignant stem cells as key to understanding the biology of many tumors and as the source of recurrence following an otherwise successful cancer treatment. Germany boasts a number of excellent research groups that have made seminal contributions to our understanding of cancer stem cell biology. One of the GSCN working groups is dedicated to bringing the expertise of these groups together under one umbrella in order to more effectively develop future therapies for cancer.

A number of tumor entities are not made up of a sing-le type of transformed cell but instead are characte-rized as consisting of a heterogeneous range of mali-

gnant cells. In a structure that resembles a classic hierarchy of normal tissues and organs, some tumors contain abnor-mal cells that, unfortunately for the patient, also exhibit the characteristic of stem cells. Increasingly, the field of cancer research is turning its sights to focus on these rare kinds of cells. Because the so-called cancer stem cell (CSC) hypo-thesis can help to explain why cells begin to proliferate and disperse, and why cancer can flare up again even after an apparently successful treatment, many scientists see CSCs as key to understanding the insidious nature of tumors.

The cause of a range of tumors

“Following the demonstration of the stem cell concept for leukemia, it has become increasingly clear that this mod-el also plays a role in many solid forms of cancer, such as carcinomas,” says Andreas Trumpp, President of the German Stem Cell Network (GSCN) and initiator of GSCN working group ‘Stem cells in diseases’. Trumpp heads the Division of Stem Cells and Cancer at the German Cancer Research Center (DKFZ) in Heidelberg. Here, several research groups are busy in-terrogating the funda-mental biology of CSCs. Other DKFZ research-ers also focus on devel-oping novel therapies that target CSCs: Hanno Glimm is investigating their role in colon cancer and Ana Martin-Villalba is developing strategies for the destruction of CSCs in glioblastoma. The impor-tant questions being pursued by the re-

searchers include: How do CSCs develop in different types of cancer? How do they promote tumor development? How can they be detected?

Terminating the survival tricks

For the field of cancer medicine, the central characteristic of CSCs is their ability to develop resistance to convention-al radio- and chemotherapy through a range of survival tricks. These resistance mechanisms are regarded as a cen-tral explanation for the phenomenon of disease relapses after treatment.

Among other work, Trumpp and his team are now trying to decode the nature of these survival tricks. In work on a leukemia mouse model conducted together with Marieke Essers, the scientist discovered so-called ‘dormant’ cancer stem cells. “Using specific cytokines, we can place these cells under stress and wake them up. They then begin to divide and thus become susceptible to chemotherapy,” ex-plains Trumpp. This serves as the basis for an effective com-bination therapy, which the Heidelberg-based scientists now want to transfer to clinical practice. Trumpp is also the managing director of the HI-STEM Heidelberg Institute for Stem Cell Technology and Experimental Medicine. To-gether with partners from hospital clinics, scientists at HI-STEM are concentrating on application- oriented research targeting tumor- and metastasis stem cells. In this way, they have succeeded in detecting and molecularly charac-terizing metastasis-inducing cancer stem cells (MICs) cir-

culating in the blood of breast cancer patients. It has been demonstrated that patients with a large

number of these cells in the blood have a particularly poor prognosis. This

work could lead to the develop-ment of detection methods for

such MICs in the blood and also provide new approach-es for the de velopment of medications for metastat-ic breast cancer.

Research network for cancer stem cells

The German Consortium for Translational Cancer

Research (DKTK), one of the six German Centers for

Health Research, is also based in Heidelberg. This makes the

city an important hub for German cancer stem cell research. The DKTK

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Stem cells in diseases (cancer stem cells)


GSCN FACHGRUPPEN | STAMMZELLEN IN KRANKHEITEN (KREBSSTAMMZELLEN)

German Cancer Research Center (DKFZ) The largest biomedical research institution in Germany

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), located in Heidelberg, is a member of the Helmholtz-As-sociation and is the largest biomedical research institute in Germany.

At the DKFZ, more than 1,000 scientists work together in order to develop novel strategies aimed at improving the prevention, diagno-sis and treatment of cancer. Several research laboratories investigate normal and cancer stem cells (CSCs) as well as their respective niches. The goal is to develop strategies to monitor and

target CSCs in primary cancers and metastasis. Together with the Dietmar Hopp Foundation, the DKFZ is a shareholder of HI-STEM, the nonprofit Heidelberg Stem Cell Institute and organizes the biannual Heinrich-Behr-Conference on „Stem Cells and Cancer“, which attracts international experts in the field. With the Heidelberg University Clinic, the DKFZ has established the National Center for Tumor Diseases (NCT), to clinically translate innovative basic cancer and stem cell research discoveries into clinical therapies.

German Cancer Research CenterIm Neuenheimer Feld 280, 69120 Heidelbergwww.dkfz.de

research program, Stem Cells in Oncology. The program combines the work of specialists from seven leading centers including research groups from Berlin, Dresden, Frankfurt/Mainz, Freiburg, Munich, Tübingen, Essen/Düsseldorf and of course the DKFZ. Within this program, intensive effort is focused on illuminating the properties of cancer and metastasis stem cells, and to develop novel therapeutic strategies to target these cells. At the Freiburg University Medical Center, the team headed by Thomas Brabletz, co-initiator of this GSCN working group, is in-vestigating the CSC concept in solid forms of cancer. He is interested in how tumors emerge in the gastrointestinal tract and the molecular changes that stimulate a cancer cell to migrate throughout the body. In pioneering work, the Freiburg-based researchers have demonstrated that specific embryonic development programs are reactivated in these kinds of cells, lending the cancer stem cells an ab-normal mobility and enabling them to spread throughout the body. Jochen Maurer in Freiburg is also concentrating

on the role of stem cells in breast cancer and on targeted treatment strategies, while Gabriele Niedermann and her team are occupied with non-invasive diagnostic methods that identify tumor stem cells in patients.

The hunt for a molecular fingerprint

Frankfurt am Main is home to several clinical research or-ganizations that are working to deepen our understanding of CSCs. A key partner in this work is the LOEWE Center for Cell and Gene Therapy, which is funded by the State of Hessen. At Frankfurt University Hospital, the team led by Michael Rieger is studying the molecular regulation of de-velopmental decisions in leukemia, breast and colon CSCs. Likewise, the team of scientists headed by Hubert Serve at the Department of Hematology and Oncology are studying leukemia stem cells, and Florian Greten (Georg-Speyer-Haus) is investigating so-called niches, namely the cellular microenvironment in the tissue in which colon cancer orig- Ph

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RESEARCH IN GERMANY | STEM CELLS IN DISEASES (CANCER STEM CELLS)

HI-STEM gGmbH is a non-profit public-private partnership between the German Cancer Research Center (DKFZ) in Heidelberg and the Dietmar Hopp Foundation (DHS).

HI-STEM performs cutting-edge research on stem cells with the aim of translating these results into novel clinical applications. This includes the development of novel diagnostic tools and innovative therapies to monitor and target leukemic and solid tumor stem cells as well as metastatic disease.

HI-STEM was founded in 2008 and is located in newly re-novated laboratories and offices within the main building of the DKFZ. The managing director of HI-STEM, Profes-sor Dr. Andreas Trumpp and five Junior Group Leaders direct an international team of more than fifty scientists, PhD/Masters students and technical staff. Together, this forms an excellent environment to perform cutting edge translational research and to train the next generation of outstanding young scientists. www.hi-stem.de

The HI-STEM Research Groups:• Hematopoietic and Leukemic Stem Cells (A. Trumpp)• Experimental Hematology (M. Milsom)• Stress induced activation of HSCs (M. Essers)• Cancer Stem Cells and Metastasis (A.Trumpp & M. Spick)• Metastatic Niches (T. Oskarsson)• Biomarker Discovery (C. Rösli)

Researchers at HI-STEM are working in close collaborati-on with colleagues of the University Clinical Centers in Heidelberg, Mannheim and other cities as well as with the National Center for Tumor Diseases (NCT) in Heidelberg. In addition, HI-STEM collaborates with various biotechnology and pharmaceutical companies to investigate and develop novel strategies to push forward the development of new drugs and effective treatments for different types of can-cer and to promote their clinical application.

inates. At the TU Dresden, Frank Buchholz is researching the important molecular switches that can transform a cell into a CSC. Junior Professor Anna Dubrovska from the Dres-den Oncology Center for Radiation Research is attempting to decipher the molecular fingerprint of CSCs and thereby to identify new biomarkers for these cells.

In Munich, Irmela Jeremia and her team at the Helmholtz Center are occupied with how leukemia stem cells are driven into programmed cell death and are examining treatment strategies against acute lymphoblastic leukemia. Heiko Hermeking at Ludwig Maximilians University is studying the molecular switches and signals that cause healthy cells to become malignant.

Forum for possible cooperation

The specialty area of the research team of Klaus Pantel from the University Medical Center Hamburg-Eppendorf is the early detection of metastasis formation through the tracking of individual tumor cells circulating in the blood. At the Institute for Tumor Biology, his team has developed a method that can trace even individual tumor cells in blood and bone marrow. A molecular profile can then be deter-mined for these cells. Such tests will help in the search for more effective treatments for patients. Finally, the team of Clemens Schmitt of the Molecular Cancer Research Center

(MKFZ) at Charité University Medicine Berlin has now demonstrated that even CSCs undergo a process of ageing. They speculate that this may be one reason why CSCs are resistant to chemo- and radiotherapy.

As well as the groups mentioned above, there are also research groups at the Institute of Reconstructive Neuro-biology in Bonn and at the university clinics in Düsseldorf and Tübingen that are closing in on disease-causing stem cells. “Overall, a very active research community has devel-oped in Germany,” says Andreas Trumpp. Alongside the US, UK and Japan, he counts Germany among the most prom-inent countries performing research in this field. Today, the GSCN working group is striving to coordinate and strengthen this expertise. “This January, we invited all oth-er interested parties from the German Stem Cell Network to a retreat organized by the DKTK,” says Trumpp. This is hoped to result in a common forum for researchers at all levels, in which they can find collaborative partners, create synergies and lay the experimental foundations for the de-velopment of effective treatment strategies. The overarch-ing goal that unites these researchers is the destruction of cancer stem cells as origins of tumors. As a result of this important work, it may be possible to gain the upper hand over CSC therapy resistance and deadly metastases.

Text: Philipp Graf


RESEARCH IN GERMANY | STEM CELLS IN REGENERATIVE THERAPIES

The basis

of regenerative medicine

diseasemodeling

Whether for direct cell and tissue replacement or as a support for the body’s self-healing powers – stem cells are a key resource for novel therapies. Rapid technolog-ical advances have already enabled a number of stem cell treatments to benefit patients. However, the great majority of therapeutic approaches currently under development are still a long way from the clinic. A new generation of translational centers has recently been established in Germany to speed developments in regener-ative medicine and a dedicated GSCN working group now aims to pool the expertise and experience necessary to move new ideas into new applications.

Healing with cells – that is the central concept of re-generative medicine. The translation of research findings out of the stem cell laboratories and into

clinical practice has caught the public imagination and raised patient expectations. However, experience has shown that the path to a scientifically sound and suffici-ently proven cell therapy is frequently long and labori-ous. To date, hematopoietic stem cell transplantation for the treatment of blood cancers is still the only stem cell therapy in routine and widespread clinical use. Even here, the procedure remains strongly dependent on the availability of suitable donors and, despite decades of ex-perience, still carries the risk of dangerous side effects. A major technical hurdle also continues to limit progress in this area: Like many other somatic stem cells, blood stem cells are difficult to expand in the laboratory.

iPS cells as game changers

Against this background, the hopes and aspirations of biomedical scientists in Germany and around the world are being pinned increasingly on the spectacular results emerging from cellular reprogramming and in particular on the isolation of induced pluripotent stem cells (iPS cells). “We certainly regard human iPS technology as a breakthrough,” says Ulrich Martin from the Leibniz Re-search Laboratories for Biotechnology and Artificial Or-gans (LEBAO) at the Hannover Medical School. Martin is one of the initiators of the GSCN working group ‘Stem cells in regenerative therapies’. Aided by iPS technology, researchers in Germany now have the means to produce pluripotent cells, cultivate them in large quantities and use them to derive specialized cell types. “It is neverthe-less clear that clinicians around the world are at the very beginning of the learning curve with regard to iPS-based cell therapies” says Martin. The first clinical trials with iPS-derived retinal pigment epithelial cells are due to be-gin in Japan in 2014. In Germany, the majority of research groups are currently focusing on alternative applications for pluripotent stem cells, primarily drug screening and

the development of culture models to enable closer inves-tigations of disease processes (see the separate chapter on page 34 ff). Ulrich Martin, however, has by no means lost sight of the therapeutic applications. His team spe-cializes in the regeneration of diseased or injured hearts. In Hannover, researchers are investigating whether iPS-derived cells can be transplanted into lesioned my-ocardial muscle, and have already gathered encouraging data in animal models. Another possible application for these cultured heart muscle cells is as a starting material for the production of bioartificial tissue constructs.

Clarifying safety aspects

Stem cell researcher Martin stresses that there are still a great many challenges to overcome. Although new pu-rification techniques make it possible to exclude almost entirely contamination of cell material with undifferen-tiated iPS cells, “Genetic mutations in the iPS cells rep-resent a major unresolved issue,” says Martin. Although these kinds of mutations could arise during cell culture, the major threat may be posed by those already present in the cells used for reprogramming. The worry here is that granting a new lease of life to mutated cells may lead to a higher incidence of malignancy. “The quest for safer cell sources or logistical solutions such as the establish-ment of cell banks is going to occupy us intensively in the future,” says Martin. Among his other activities, Mar-tin is involved in the development of clinically safer cell products from umbilical cord blood, and of new tools for the correction of genetic defects in patient-specific stem cells.

Spotlight on somatic stem cells

As a consequence of the ethical and legal climate and the resulting funding policies, biomedical researchers in Germany have traditionally concentrated more on the therapeutic potential of somatic stem cells. Michael Cross, who heads the hematological stem cell laboratory at the University Hospital in Leipzig, is co-initiator of the GSCN working group. Cross sees a continuing increase in national activity in this area most noticeably with respect to mesenchymal stem cells (MSCs). “At the first GSCN an-nual conference, a third of the poster contributions for regenerative therapies were from this area,” says Cross. MSCs are popular not only because they can develop into cartilage, bone, muscle and adipose tissue, but also be-cause they mitigate inflammatory and immune respons-es and can support the development of blood progenitor cells in the bone marrow. Germany is also strong in the hematopoietic stem cell field, with extensive experience and healthy cooperation between specialized clinics,

Stem cells in regenerative therapies


GSCN FACHGRUPPEN | STAMMZELLEN IN REGENERATIVEN THERAPIEN

of regenerative medicine



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Bioartifical cardiac tissue (BCT) in a bioreactor


FORSCHUNG IN DEUTSCHLAND | STAMMZELLEN IN REGENERATIVEN THERAPIEN

The REBIRTH Cluster of ExcellenceFrom Regenerative Biology to Reconstructive Therapy

REBIRTH has, under the nationwide Excellence In-itiative, been funded as a cluster of excellence since 2006. Its aim is to develop innovative therapies for the heart, liver, lungs and blood, and to translate these into clinical use. This involves collabora-tion – in Hannover and at participating partner institutions – between physicians, physicists, che-mists, biologists, engineers, legal professionals and ethicists, the main research priorities being stem cell biology, the reprogramming of cells for cell the-rapy, disease models and tissue engineering. The review process prior to the second funding period showed that REBIRTH has successfully established itself as an internationally renowned centre for re generative medicine.

Participating Partners: - Hannover Medical School- Leibniz University of Hannover- Hannover Laser Centre- University of Veterinary Medicine Hannover,

Foundation- Helmholtz Centre for Infection Research Braun-

schweig- Max Planck Institute for Molecular Biomedicine,

Münster- Institute of Farm Animal Genetics, Friedrich Loeffler

Institute, Mariensee- Fraunhofer Institute of Toxicology and Experimental

Medicine, Hannover

REBIRTH Cluster of ExcellenceHannover Medical SchoolCarl-Neuberg-Straße 1, 30625 Hannoverwww.rebirth-hannover.de

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many of which are actively involved in research in this area. “The field of gene therapy is also experiencing something of a renaissance,” says Cross.

Translational research into cell therapies

Anybody looking for an expert in cell-based thera-pies in Germany would be wise to head for one of the translation centers for regenerative medicine. These centers place a strong emphasis on interdisciplinarity and combine basic and applied research to establish a scientific platform for the development of future ther-apies. Their construction has been promoted over the past ten years by the German Federal Ministry of Edu-cation and Research (BMBF) and the German Research Foundation (DFG). There are now five major transla-tional centers with a focus on regenerative medicine – in Hannover, Berlin, Dresden, Rostock, and Leipzig. In addition, regional initiatives have led to the establish-ment of further centres for cell-based therapies in the southern and western regions of Germany including Stuttgart and Tübingen, around Frankfurt am Main and in Würzburg.

In Hannover, the DFG-financed Cluster of Excellence REBIRTH, brings together a total of seven local research institutions in an initiative that is coordinated by the Hannover Medical School and that focuses pri marily on diseases of the blood, heart, lungs and liver. The Berlin-Brandenburg Center for Regenerative Therapies (BCRT), led by Hans-Dieter Volk, is supported by the BMBF, the federal states of Berlin and Brandenburg, the Berlin University Charité hospital and the Helmholtz Association. Research here is concentrated in four major areas: the immune-, cardiovascular-, nervous- and mus-culoskeletal-systems. Leipzig is home to the Transla tional Center for Regenerative Medicine (TRM). This center, which is funded by the BMBF, the State of Saxony and the University of Leipzig, works closely with the Fraunhofer Institute for Cell Therapy and Immunology (IZI). One of the research areas of the TRM is dedicated exclusively to cell therapies, approaching a wide spectrum of degene-rative diseases of the nervous system, the skin and the musculoskeletal system. Director of the TRM Leipzig and Fraunhofer IZI is Frank Emmrich, who is also one of the initiators of a GSCN strategic working group on stem cell technologies.


RESEARCH IN GERMANY | STEM CELLS IN REGENERATIVE THERAPIES

Berlin-Brandenburg Center for Regenerative TherapiesBCRT

The Berlin-Brandenburg Center for Regenera-tive Therapies (BCRT) is an interdisciplinary translational center with the goal of enhancing endogenous regeneration by cells, biomaterials, and factors which can be used to develop and implement innovative therapies and products. At the BCRT clinicians and researchers are wor-king closely together on a personalized medicine that depends on the early recognition of patients‘ individual healing potential. The primary focus of the BCRT is on diseases of the immune system, the musculoskeletal system, the cardiovascular system

and the kidney for which currently only unsatisfac-tory treatment options are available. Early coope-ration with industry, health insurers and regulatory authorities as well as other external partners boosts the chances of exploiting new methods and provides access to flexible financing options.

BCRT · Charité - Universitätsmedizin BerlinAugustenburger Platz 1, 13353 Berlinwww.b-crt.de

A further important location in Saxony is the DFG-fund-ed Center for Regenerative Therapies Dresden (CRTD). Here, studies are underway into the use of stem cell-based therapies for five medical indications: hematologi-cal diseases, diabetes, neurodegenerative diseases, bone and cartilage replacement, and cardiovascular diseases. For it’s part, the Reference and Translation Center for Cardiac Stem Cell Therapy (RTC) in Rostock is focused exclusively on clinical testing of a specific cell therapy for heart disease in the multicenter clinical trial known as “PERFECT”. In this trial, coordinated by Gustav Stein-hoff, CD133+ cells from the bone marrow are isolated from cardiac patients during a bypass operation and re-injected into the heart muscle. It is the hope of re-searchers that once inside the body and secreting a mix of molecules, these cells will boost the regeneration of the affected area. The Health Region REGiNA between Stuttgart and Tübingen has also established itself as a translation location for cell-based therapies. The LOEWE Center for Cell and Gene Therapy in Frankfurt, found-ed as part of a regional Excellence Initiative in Hessen, develops innovative therapies for clinical application, particular for cardiovascular and hematological diseas-es. In Munich, numerous university clinics and the local Helmholtz Center are working on the development of cell therapies. A new Fraunhofer Translation Center for medical products and cell-based regenerative therapies

is in the planning stages in Würzburg. Finally, the region of North Rhine-Westphalia is also emerging as a power-house for research into the technologies and cell sources for the stem cell therapies of the future, with activities in Aachen, Bochum, Bonn, Düsseldorf, Cologne and Mün-ster.

Raising awareness of regulatory issues

The GSCN working group provides an opportunity for experts and young scientists from the various research centers to benefit from each other’s experience, exper-tise and resources, says Martin. This forum should also encourage new collaborations at the national and inter-national level. Some researchers are already involved in EU networks or Ministry-funded collaborations with stem cell researchers in the United States developing strategies for future cell-based treatments. There is also the matter of raising awareness of the many studies and approval issues that lie ahead: “It is important to be prepared for a lengthy process and to deal with approval-relevant is-sues in a timely manner,” stresses Martin. To address such questions, the GSCN has established a strategic working group ‘Clinical trials and regulatory affairs’. Initiators are Berlin-based researchers Hans- Dieter Volk and Andreas Kurtz, as well as Torsten Tonn from the medical faculty of the TU Dresden. Text: Philipp Graf

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RESEARCH IN GERMANY | STEM CELLS IN DISEASE MODELING & DRUG DEVELOPMENT

Personalized medicinein the Petri dish



disease modeling

drug developmentre-programming

re-programming

Somatic stem cell

The increasing availability of pluripotent stem cells is set to change the face of health research. In human cell systems, for example, they have already greatly advanced the study of the molecular causes of disease, and cell models or miniature organs in the culture dish are regarded as important tools for expediting toxico-logical testing and drug discovery in the pharmaceuti-cal industry. German stem cell researchers contribute significantly to this global development towards the establishment of personalized medicine.

Public awareness of stem cells appears to be focused in particular on their application in regenerative therapies. For the most part, however, such treat-

ments require an extremely lengthy development pro-cess and take a long time to reach patients. Nonetheless, the first major applications to use pluripotent stem cells promise to become reality in the foreseeable future – a prospect of which many experts and even Nobel Prize winner Shinya Yamanaka are convinced. In this case, it is in the form of a culture dish-based cellular disease model and the subsequent possibilities for drug screening in the pharma industry.

The modern technologies now emerging from stem cell laboratories are opening up new means of exploring the molecular causes of diseases in areas previously lacking direct access to cell material. “These include diseases of the nervous system, the heart or insulin-producing cells in the pancreas,” says Oliver Brüstle from the Institute of Reconstructive Neurobiology at the University of Bonn. The GSCN founding president is also one of the initiators of the scientific working group “Stem cells in disease modeling & drug development”.

Patient genomes captured in cells

This development has been spurred by pioneering advances such as the generation of induced pluripotent stem (iPS) cells and the findings that have emerged from the field of direct programming. The advantage of repro-gramming is that it enables the propagation of patient cells in a Petri dish. In later steps, these are converted into cell types that are relevant for the disease in question (see graphic on page 33). These cells, which carry the genome of a patient, open up new perspectives into the molecu-lar causes of diseases. For the first time, cell researchers have the possibility of developing patient-specific cell models in an ‘authentic’ human background. These cells are useful both for the observation of disease-causing mechanisms and for the study of the effects of specific

active substances. Stem cell research is thus set to bring about major advancements in the emerging treatment concept of ‘personalized medicine’.

Stem cells for high-throughput screening

Other technological breakthroughs are opening up en-tirely new possibilities for the industrial application of stem cells − for the pharma industry, the ability to pro-duce defined human cell types in large quantities is a powerful new premise in the search for novel drugs. Also in pre-clinical toxicological assessments, mass-produced human cell cultures carry great promise as a tool for the minimization of animal testing. At the same time, they make the tests more ‘human-specific’.

Pharma industry: looking on with interest

The iPS revolution has even brought about a change in thinking in the pharma industry, where attitudes towards stem cells were previously extremely hesitant. Today, the majority of large companies have greatly expanded their research activities in the field. This growth in interest is also reflected in the cooperation projects currently being pursued by the European Innovative Medicines Initiative (IMI). In the shape of StemBANCC and EBiSC, there are two large consortia providing a base for collaborations between pharmaceutical companies and European re-search institutions. StemBANCC, which launched in 2013 with a budget of almost €55 million, is working to pro-duce 1,500 human iPS cell lines, in particular for neuro-degenerative diseases and diabetes. In the framework of EBiSC, the European Union and partners are contributing €35 million for the construction of a major European iPS cell bank and the cataloguing of over 10,000 patient-spe-cific cell lines. Both consortia include the participation of German stem cell researchers and research institutions.

Research landscape for disease models

Among these is a team of neurogeneticists that is headed by Christine Klein from the University Hospital in Lübeck and which is specialized in the research of hereditary forms of specific neurodegenerative diseases, in par-ticular Parkinson’s. In the StemBANCC project, they are coordinating the establishment of a sample bank of skin samples from 500 Parkinson’s patients from across Eu-rope. To gain a clearer picture of the basic mechanisms of Parkinson’s disease, the researchers are working to draw comparisons between iPS cells from patients and healthy cells and thereby shed light on the mechanisms that pro-mote cell death.

Stem cells in disease modeling & drug development



Institute of Reconstructive NeurobiologyFrom disease modeling to stem cell therapies

The Institute of Reconstructive Neurobiol-ogy at the University of Bonn Medical Centre focuses on the use of pluripotent stem cells for the study and treatment of neurological dis-orders. Based on a broad technology portfolio including cell reprogramming, neural differ-entiation, direct cell fate conversion, stem cell industrialization and neurotransplantation, the Institute develops stem cell-based model systems for disease-related research and drug development as well as novel cell therapy reg-imens. It closely interacts with LIFE&BRAIN

GmbH, a translational hub of the University of Bonn providing stem cell products and services for pharma, biotech and academia.

Institute of Reconstructive NeurobiologyLIFE&BRAIN GmbHUniversity of Bonn Sigmund-Freud-Strasse 2553105 Bonnwww.stemcells.uni-bonn.de

At the Institute of Reconstructive Neurobiology at the University of Bonn, Philipp Koch – a member of Oliver Brüstle’s team – has developed an important cellular tool for the development of disease models. Here, the re-searchers are using human embryonic stem (ES) cells to derive neural stem cells, also known as lt-NES cells. With standardized protocols, these multipotent cells can be used to quickly and reliably generate a range of defined cell types of the central nervous system. Likewise, lt-NES cells can be derived from iPS cells. “This provides us with a path for patient-specific disease models,” explains Brüs-tle. The Bonn-based scientists have already employed this approach to elucidate the pathogenic mechanisms in Machado-Joseph disease. Moreover, aided by neurons from Alzheimer’s patients, they have demonstrated that such cell systems can assist in predictions on the efficacy of drugs.

Intensive work at German laboratories

Numerous researchers in Germany are already utilizing patient-specific cell models to place neurodegenerative diseases under far closer scrutiny than was previously possible. One of them is Jared Sterneckert at the Max Planck Institute for Molecular Biomedicine in Münster, who is focusing on the mechanisms of Parkinson’s dis-ease. The Bavarian Research Network “ForIPS”, which

was launched last year, aims at using iPS cell-derived dis-ease models to analyze the pathogenesis of Parkinson’s disease in particular. Spokesperson is Erlangen-based neurobiologist Jürgen Winkler. At the university clinic Erlangen, Beate Winner and her group are occupied with the pathogenic mechanisms of Parkinson’s and other neurological illnesses.

Stefan Liebau from the Department of Neuroanatomy at the University of Tübingen is employing iPS cells to study motor neuron synapses in patients with muscle weakness. For the future, he is planning to cultivate ret-inal cells to be used for an improved understanding of the molecular background of degenerative retinal disor-ders. Suzanne Kadereit from the University of Konstanz is developing cell models that will be employed to test substances for potential neurotoxic effects.

The study of cardiovascular disease in cell cultures is just one of the specialty areas of Karl-Ludwig Laugwitz from the TU Munich’s Klinikum rechts der Isar University Hos-pital. His team is using patient-specific stem cell models to search, among other things, for the molecular back-ground to cardiac arrhythmias. Laugwitz is co-initiator of the GSCN working group. The groups headed by Ulrich Martin at the REBIRTH Cluster of Excellence at the Med-ical School Hannover (MHH) and Jürgen Hescheler at the University of Cologne are scrutinizing iPS cell-derived heart muscle cells for use in pharmacological testing. The working group of pharmacologist Thomas Eschen-hagen from the University Medical Center Hamburg-Ep-pendorf are developing similar heart muscle models for the testing of individual genetic defects and therapies. The long-term objective is the development of an auto-mated process to assist in predictions about individual susceptibility to heart failure and to facilitate treatment decisions.

At REBIRTH/MHH, Tobias Cantz is concentrating on dis-eases of the liver. Cantz, who heads a Hannover-based group of Münster’s Max Planck Institute for Molecular Biomedicine, is using iPS technology to produce pa-tient-specific hepatocytes for the detailed study of the molecular processes of metabolic liver diseases.

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Stem cells help develop cellular models for understanding Parkinson’s disease

Recently, Life Technologies partnered with the Parkinson’s Institute in Sunnyvale, CA, to develop Parkinson’s disease (PD) model systems using donor fibroblasts that have been collected at the Institute. Induced pluripotent stem cells (iPSCs) were generated and evaluated using both cellular and genetic analysis tools to confirm successful reprogramming. The establishment of these fully characterized iPSC lines, from samples with known clinical histories, sets the stage for further disease-relevant studies. With this work, we hope to demonstrate how systems can be developed to identify drugs that may ameliorate the processes that underlie PD, or to understand the environmental factors that impact the development of PD.

What is Parkinson’s disease?

Parkinson’s disease is a progressive neurodegenerative disorder that affects 1% of people over age 60 and more than 5 million people worldwide [1]. PD results primarily from the selective loss of dopaminergic neurons, which first affects movement, but then later affects cognitive function, with late-stage disease often being accompanied by dementia. The absence of physiologically relevant cellular models for PD represents a major bottleneck for PD research. Novel models are urgently needed to accelerate the discovery of disease mechanisms and drug targets, which could rapidly translate into a wide range of clinical and therapeutic applications.

Modeling a neurodegenerative disease

Download the publication to read the details on:

• Reprogramming of donor fibroblasts• Characterization of iPSCs by antibody staining and flow analysis• Gene expression analysis of the iPSCs and donor fibroblasts• Evaluation of expression of reprogramming transgenes• Cell line authentication

Please visit lifetechnologies.com/parkinsons to download the paper.References1. Olanow CW, Stern MB, Sethi, K (2009)The scientific and clinical basis for the treatment of Parkinson disease. Neurology 72(21 Suppl 4):S1–136.

Alongside the study of disease in the culture dish, a fur-ther important venture of Oliver Brüstle and his team in Bonn is the manufacture of cell products and the indus-trial-scale testing of active substances. In cooperation with the Fraunhofer Institute for Production Technolo-gy IPT and RWTH Aachen, a manufacturing system has recently been implemented at the LIFE&BRAIN research center. It enables the automated production of iPS cells and their differentiation into neural cells or cardiomyo-cytes. Further research institutes and companies based in North Rhine-Westphalia also participate in the joint project. “Our StemCellFactory is a fully automated pro-duction line for iPS cells and their derivatives,” says Brüs-tle. The industrial application of stem cells in compound screening also requires new methods of high-throughput imaging, such as those being developed by Sabrina Des-bordes at the Institute of Developmental Genetics of the Helmholtz Center Munich.

Boosting translation

This compact overview only partly reflects the diverse research activities underway in Germany in this field. Today, the GSCN working group is involved heavily with pooling and highlighting this national expertise. “We want to establish a research map that will serve as guid-

ance for scientists but also for interested biotech- and pharmaceutical compa-nies, and thereby improve interexchange between the various stakeholders,” says Brüstle. Numerous German pharmaceutical companies have already signaled their interest: “The opportunity to gain patient- and disease-specific stem cells has raised great hopes in the pharmaceutical industry for more predictive and efficient cell systems for drug development,” says Ralf Heilker, who works in the Department of Lead Structure Identification at Boehringer Ingelheim’s Biberach site.

Brüstle, who is in no doubt that stem cell-based disease models will play a key role in future drug development, emphasizes the importance of forging early alliances with biotech and pharma for the speedy transfer of stem cell research into the healthcare industry.

Text: Philipp Graf

Cardiomyocytes from human induced pluripotent stem cells

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RESEARCH IN GERMANY | COMPUTATIONAL STEM CELL BIOLOGY’


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The field of experimental stem cell research is producing a flood of data that would be impossible to manage without computational support. This discipline of bio informatics for the analysis and organization of biological data is one of many related fields that are indispensable for modern stem cell research. Systems biologists are using mathe-matical models and computer simulations to delve deeper than ever before into the fascinating properties of stem cells. A growing number of specialists in Germany are dedicating themselves to the computational view of stem cells, and are in the process of changing the face of clinical research.

Understanding the behavior of – and lending an element of predictability – to stem cells: this is the objective of a growing body of systems

biologists, mathematicians and computer scientists active in the field in Germany. The possibilities for the computer-based analysis of experimental data have im-proved significantly in the past ten years. “We now have the modern technologies needed to collect a sufficient amount of quality data. These give us the experimental basis to test our stem cell models,” says Ingo Röder from the Institute for Medical Informatics and Biometry (IMB) at the Technical University of Dresden. In the mathema-tician’s opinion, there is a growing acceptance among his colleagues to also bring the ‘theorists’ on board in the planning of studies. Molecular biologists and physicians are recognizing that theoretical approaches can provide impetus not only for fundamental insights but also for eventual clinical application. At the same time, it is clear that the avalanche of data produced by molecular biolo-gy laboratories, such as from high-throughput analyses, can only be properly managed with the help of serious computing power and methods of bioinformatics.

The dynamic cell

Together with Rostock-based bioinformatician Georg Fuellen, Ingo Röder is one of the initiators of the GSCN working group ‘Computational methods stem cell biolo-gy.’ Röder’s working group has been engaged for some years with the mathematical modeling of stem cell sys-tems. His team is focusing on the adult stem cells of the blood-forming system – the hematopoietic stem cells (HSCs). In particular, the researchers are hoping to un-derstand how HSCs alternate between different cellular states. In recent years, they have built up a clear picture of the dynamic decision-making processes that take place during the transition to different cell states, name-ly a flexible switching back and forth between molecular states. “Very early on, we predicted from our mathemati-cal models that two states exist in HSCs: dormant and ac-

tive cells, which can divide and multiply,” explains Röder. Physicians and stem cell biologists have now experimen-tally confirmed these predictions. “These data help us to further develop existing models and to sharpen our hypotheses,” says Röder. In the case of a blood cancer disease, his team has already demonstrated how a theo-retical HSC model can be transferred to clinical practice: an important role in Chronic Myeloid Leukemia (CML) is played by ‘dormant’ stem cells, which are unaffected by treatment. There is thus a hypothesis that these dormant cancer stem cells could be reactivated and, in combina-tion with other substances, attacked more effectively through treatment with cell cycle-stimulating agents such as IFN-α. This would not only increase the effective-ness of a therapy but would also reduce the risk of the re-currence of the disease following a successful treatment. “With our computer program, we can run through the possibilities of such a therapy in a range of different con-ditions.” Röder is certain that in the medium term, such calculations will be decisive in improving the design of clinical trials. Real world examples already exist for how patients can benefit from the findings of the Dresden stem cell mathematician, for example predictions about different drug dosages and the duration of a specific therapy. “In collaboration with clinicians in Mannheim and Jena, we have already successfully used our models to predict the clinical course of a CML treatment with the drug Imatinib.” This also allows prognoses to be made on the optimal time for a patient to end a course of therapy.

German stem cell modelers

In Dresden, Ingmar Glauche has put together a junior group for systems biology that is likewise occupied with these and related issues of HSCs. Other dedicated stem cell modelers are also at work at the University of Leip-zig. There, the head of the Institute for Medical Informat-ics, Statistics and Epidemiology, Markus Löffler, togeth-er with Jörg Galle, group leader at the Interdisciplinary Center for Bioinformatics, specializes in simulations and models of the behavior of intestinal stem cells in tissue niches, i.e. the microenvironment in which they are em-bedded. Stem cell phenomena is a priority research area for the team headed by Fabian Theis, Chair of Computa-tional Modeling in Biology at the TU Munich. Here, the mathematician Theis is working on single-cell analysis, which is also highly relevant for stem cell biologists. Such technologies for the analysis of individual cells are becoming progressively more sophisticated but remain extremely laborious. Moreover, the specific handling of cells can be the cause of significant measurement inac-curacies. The consequence of this is random statistical noise in analysis, which can swamp the sought-after fine



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RESEARCH IN GERMANY | COMPUTATIONAL STEM CELL BIOLOGY’

Max Planck Institute for Molecular GeneticsMPIMG

MPIMG

Research at the Max Planck Institute for Molec-ular Genetics (MPIMG) concentrates on genome analysis of man and other organisms to contrib-ute to a global understanding of many biological processes in the organism, and to elucidate the mechanism behind many human diseases.

It is the overall goal of all MPIMG’s groups to gain new insights into the development of dis-eases on a molecular level, thus contributing to the development of cause-related new medical treatments. In this context, stem cell research

is gaining increasing importance. In particular, MPIMG researchers are working on a better un-derstanding of gene regulation networks for tissue formation and homeostasis, as their dysfunction may result in numerous diseases

Max Planck Institute for Molecular GeneticsIhnestraße 63-73, 14195 Berlinwww.molgen.mpg.de

distinctions in the data, for example information relating to gene regulation. One solution under consideration by Theis and his team is the study of larger samples, each of ten cells. Aided by statistical methods, this enables the calculation of significantly more accurate results – an outcome already proven in experimental studies. Researchers in Berlin, Freiburg, Plön, Heidelberg and Aachen are likewise – though not exclusively – occupied with mathematical models for stem cell biology.

Digital magnifier for pluripotency

The stem cell development program is influenced by a complex interplay of transcription factors, sig-naling molecules and epigenetic mechanisms. The high-throughput analyses that aim to shed light on these aspects are producing vast quantities of data. These data, which originate in particular from genome-, tran-scriptome- and proteome analyses, must be evaluated, integrated and interpreted. So what connects the various regulatory components in stem cells? And what are the relationships between them? These questions require the know-how of bioinformatics. Today, numerous loca-tions across Germany are specialized in the data analysis of the molecular processes in stem cells. Together with his team, Georg Fuellen, head of the Institute for Bio-statistics & Informatics in Medicine & Ageing Research,

has developed the ‘PluriNetWork’ database and the soft-ware ’ExprEssence’. These tools enable the even closer scrutiny of interactions between hundreds of genes and proteins, such as in the induction of pluripotency or during the first steps of cell differentiation. Once more is known about them, the processes can be chemically influenced. It is anticipated that the innovative methods of bioinformatics will markedly improve the search for suitable drug candidates. With the assistance of corre-sponding algorithms, it is also possible to analyze combi-nations of drug candidates for their effects. The research work being carried out by Marcos Araúzo-Bravo at the Max Planck Institute for Molecular Biomedicine in Mün-ster is aimed at deciphering the complex ensemble of transcription factors and their target structures in stem cells. Araúzo-Bravo’s team has developed algorithms for the analysis of the epigenetic fingerprint of pluripotent stem cells. At the Max Delbrück Center in Berlin-Buch, Miguel Andrade’s working group is specialized in data analyses of the stem cell system. At the Max Planck In-stitute for Molecular Genetics in Berlin, Martin Vingron’s team also aims at the elucidation of pluripotency with bioinformatical approaches. Bioinformatics methods for the analysis of stem cells are also being developed by researchers at research institutions in Aachen, Cologne, Munich and Saarbrücken.

“Our GSCN working group aims to raise awareness of the value of theoretical models for biological questions. We want to more strongly introduce our ideas into the community,” says Ingo Röder, who sees the working group as a possible point of contact for stem cell biolo-gists, both to exchange ideas and to launch bilateral pro-jects. All of which is intended to bring us ever closer to the fascinating properties of stem cells. Text: Philipp Graf

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GSCN | ANNUAL REPORT

GSCNAnnual Report

Mission und SynopsisMissionThe German Stem Cell Network (GSCN) aims to create synergies between all areas of basic and applied stem cell research and to provide an interface between science, education, politics and society as a whole.

SynopsisThe central task of the GSCN is to pool expertise in stem cell research in Germany and develop synergies between basic research, regenerative medicine and pharmacology. The initiative will promote innovative research activities on a national and international level. In addition, targeted information and events will be developed to encourage public discourse on stem cell research.

BoardsExecutive BoardAccording to Section 8 (1) of the statute of the German Stem Cell Network (GSCN), the Executive Board is comprised of the Acting President (Chair), the Senior President (1st Vice Chair), the Designated President (2nd Vice Chair), the Treasurer and an Assessor. During the reporting period (November 2013 – Novem-ber 2014), the Executive Board is made up of the following people:

Acting President (Chair)

Prof. Dr. Andreas Trumpp (DKFZ Heidelberg)E-mail: [email protected]

Senior and Founding President (1st Vice Chair)

Prof. Dr. Oliver Brüstle (University of Bonn)E-mail: [email protected]

Designated President (2nd Vice Chair)

Prof. Dr. Dr. Thomas Braun (MPI f. Heart and Lung Research, Bad Nauheim)E-mail: [email protected]

Treasurer Dr. Michael Cross (University of Leipzig)E-mail: [email protected]

Assessor Prof. Dr. Frank Emmrich(TRM & University of Leipzig)E-mail: [email protected]

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Executive Board of the founding period 2013The GSCN offers its sincere thanks to the members of the Executive Board during the founding period (May 2013 – November 2013):

Acting President Prof. Dr. Oliver Brüstle

Senior President (from Nov. 2013 in the Extended Board)

Prof. Dr. Albrecht Müller (University of Würzburg)E-mail: [email protected]

Designated President Prof. Dr. Andreas Trumpp

Treasurer (fom Nov. 2013 provisional Managing Director)

Dr. Daniel Besser (GSCN & MDC, Berlin)E-mail: [email protected]

Assessor Prof. Dr. Frank Emmrich

Extended BoardAccording to Section 9 (1) of the statute of the GSCN, the Extended Board comprises up to 15 people. Through decision of the Founding Meeting on May 7, 2013, all founding members not elected to the Ex-ecutive Board were appointed to the Extended Board. During the reporting period, the Extended Board is constituted of the following people:

PD Dr. Tobias Cantz (MH Hannover)E-mail: [email protected]

Dr. Micha Drukker1 (Helmholtz Cent. Munich)E-mail: [email protected]

Prof. Dr. Magdalena Götz (LMU Munich)E-mail: [email protected]

Ira Herrmann (Stem Cell Network NRW)E-mail: [email protected]

Prof. Dr. Jürgen Hescheler (Univ. of Cologne)E-mail: [email protected]

Prof. Dr. Ulrich Martin (MH Hannover )E-mail: [email protected]

Prof. Dr. Ana Martin-Villalba1 (DKFZ Heidelberg)E-mail: [email protected]

Prof. Dr. Albrecht Müller1

Prof. Dr. Hans R. Schöler (MPI for mol. Biomed.)E-mail: [email protected]

Prof. Dr. Elly Tanaka (CRT Dresden)E-Mail: [email protected]

Prof. Dr. Mathias Treier (MDC, Berlin)E-Mail: [email protected]

1 from November 2013

Founding members of the executive board: A. Trumpp, F. Emmrich, O. Brüstle, D. Besser (absent: A. Müller)



Working Group InitiatorsScientific working groups

Pluripotency and re-programing Dr. Micha Drukker Prof. Dr. Hans Schöler Prof. Dr. Mathias Treier

Somatic stem cells and development Prof. Dr. Dr. Thomas Braun Prof. Dr. Elly Tanaka

Stem cells and diseases (cancer stem cells)

Prof. Dr. Thomas Brabletz (University of Freiburg)E-mail: [email protected]. Dr. Andreas Trumpp

Stem cells in regenerative therapies Dr. Michael CrossProf. Dr. Ulrich Martin

Stem cells in disease modeling and drug development

Prof. Dr. Oliver BrüstleProf. Dr. Karl-Ludwig Laugwitz (Clinic r.d.I. TU Munich)E-mail: [email protected]

Computational stem cell biology Prof. Dr. Georg Fuellen (IBIMA Rostock)E-mail: [email protected]. Dr. Ingo Röder (TU Dresden)E-mail: [email protected]

Strategic working groups

Funding programs and policies Prof. Dr. Ulrich MartinProf. Dr. Albrecht MüllerActing GSCN President (ex officio)

Career development Prof. Dr. Hartmut Geiger (University of Ulm)E-mail: [email protected]. Dr. Jürgen HeschelerDr. Insa Schröder (GSI Helmholtzz. f. Schwerion.forsch.)E-mail: [email protected]

Public engagement and outreach activities

PD Dr. Tobias CantzIra Herrmann

Patient information (stem cell therapies)

Dr. Gisela Badura-Lotter (University of Ulm)E-mail: [email protected] Herrmann

Clinical trials and regulatory affairs

Dr. Andreas Kurtz (BCRT Berlin)E-mail: [email protected]. Dr. Torsten Tonn (Inst. f. Transfus. Med. Dresden)E-mail: [email protected]. Dr. Hans-Dieter Volk (BCRT Berlin)E-mail: [email protected]

Stem cell technologies Dr. Andreas Bosio (Miltenyi, Bergisch Gladbach)E-mail: [email protected]. Dr. Frank Emmrich



Facts and FiguresMeetings

Meetings of the Founding Committee• Meeting of the Founding Committee on March 20, 2013 in Frankfurt • GSCN Kick-off Meeting on April 24, 2013 in Cologne• Founding Meeting on May 7, 2013 in Frankfurt

Meetings of the Executive BoardThe Board of the GSCN meets at regular intervals or takes part in telephone conferences. The meetings are coordinated and organized by the coordination office. The following meetings of the Executive Board took place during the reporting year:• Video conferences (June 6/13 and July 22, 2013)• November 11, 2013 in Berlin

Meetings of the Extended Board• November 11, 2013 in Berlin

Members’ Meeting • November 12, 2013 in Berlin

Overview of members in 2014

Total members 287

Natural persons Full members 168

Students 99

Corporate bodies Research institutes 12

Companies > 20 members in full-time employment 2

Companies ≤ 20 members in full-time employment 5

Partner societies 1

Members of the working groups

Scientific working groups Pluripotency and re-programing 156

Somatic stem cells and development 126

Stem cells in diseases (cancer stem cells) 124

Stem cells in regenerative therapies 152

Stem cells in disease modeling and drug development 110

Computational stem cell biology 6

Strategic working groups Funding programs and policies 107

Career development 105

Public engagement and outreach activities 88

Patient information (stem cell therapies) 62

Clinical trials and regulatory affairs 16

Stem cell technologies 157

As of 02/28/2014



Institute members• Berlin-Brandenburg Center for Regenerative Therapies (BCRT)• Center for Regenerative Therapies Dresden (CRTD)• German Cancer Research Center, Heidelberg (DKFZ)• Fraunhofer Institution for Marine Biotechnology (Fraunhofer EMB), Lübeck• Fraunhofer Institute for Cell Therapies and Immunology (Fraunhofer IZI), Leipzig• Institute for Reconstructive Neurobiology, University of Bonn• Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch • Max Planck Institute for Heart and Lung Research (MPI-HLR), Bad Nauheim• Max Planck Institute for Molecular Genetics (MPIMG), Berlin• Rebirth Cluster of Excellence, Hannover Medical School• SFB 873, Centre for Organismal Studies (COS), Heidelberg• Tissue Engineering and Regenerative Medicine (TERM), University Clinic Würzburg

Company members• AMS Biotechnology (Europe) Ltd.• Eppendorf AG• Essen BioScience Ltd.• HI-STEM gGmbH• Life Technologies GmbH• PELOBiotech GmbH

Partner Societies• Deutsche Gesellschaft für Transfusionsmedizin und Immunhämatologie (DGTI) e.V.

(German Society for Transfusion Medicine and Immunohematology)

Foundation and Structure of the GSCNBased on a call by the Federal Ministry of Education and Research (BMBF) to “set up a discussion plat-form for stem cell research,” the GSCN was founded as a registered association (e.V. = einge tragener Verein) in Berlin on May 7, 2013 and on September 25, 2013 was entered in the register of associa-tions at the local court of Charlottenburg/Berlin under the number VR 32698 B. The objective of the association is to promote science, research and education, in particular in the field of stem cell research, basic research and their application. Individual tasks and purposes derive from the stat-ute of the GSCN. The GSCN’s current statutes of July 2013 can be downloaded from the GSCN website (www.gscn.org). Ph

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Founding meeting on May 7, 2014; from left:: U. Martin, F. Emmrich, M. Treier, I. Herrmann, O. Brüstle, E. Tanaka, D. Besser, A. Trumpp, T. Cantz, H. Schöler

GSCN Homepage „www.gscn.org“

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The founding of the GSCN was preceded by a national discourse with German cell stem researchers on the content and objectives of the GSCN, which took place during a meeting of the founding committee in Frankfurt (March 20, 2013) and through online surveys (April 15 – June 30, 2013). 148 scientists, 13 institutes and 20 companies took part in the online surveys. 81% of those surveyed said that it was highly likely they would want to become members of the GSCN, with 69% prepared to engage actively in working groups (37%) and committees (25%). The organization of an annual conference was considered to be very important by 88% of those surveyed. The high number of scientists attending the 1st Annual Conference of the GSCN (November 11 – 13, 2013) also indicates the need for networking in general and in particular for the opportunity to exchange ideas and information on specific topics.

Members began joining in July 2013; by February 2014 the total had reached 287. Following members’ suggestions, during the reporting period the Executive Board set up six scientific and six strategic work-ing groups which are led by the initiators. In the future they will be supervised by coordinators who are appointed jointly by the Executive and Extended Boards or who are elected by the members of the working groups

CommunicationAn initial flyer about the network and a temporary website were published in April 2013; the website was relaunched on October 8, 2013. The network’s website (www.gscn.org) is designed to address the various target groups (scientists, members, journalists, patients, the public) and provide them with appropriate information. The click rate for the GSCN website far exceeded expectations, even consid-ering the extensive range of information that it offered, with 13,600 visits from 6,300 different visitors (IP addresses). It is used nationally (74% of visitors) and internationally (26%). Since December 2013, nine short films have been made about the work and structure of the GSCN. They are available on the GSCN website and include a film with highlights of the 1st Annual Conference of the GSCN, brief inter-views with Oliver Brüstle on the founding of the GSCN, Andreas Trumpp on the future of the GSCN, Tobias Cantz on outreach programs, Frank Emmrich on regenerative medicine and stem cell research, Insa Schröder on career development, Elly Tanaka on international interactions, Daniel Besser on the structure of the GSCN, and Albrecht Müller on the situation of funding for stem cell research. By March 2014 the films had been viewed more than 530 times and they illustrate the design of the overall com-munication concept.

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Interaction of the members is already possible to a degree with the GSCN members’ portal (www.vere-inonline.org/GSCN) to ensure a dynamic exchange of information. Every member can set up a profile in the members’ portal and can update and customize it at any time. The members decide themselves what data should be visible to other members. This profile can also be used for changes to an individ-ual’s affiliation to working groups. There is a simple discussion forum where members can communi-cate with each other individually and within the working groups. It is also possible to call up the lists of members for individual working groups and the profiles of the other members; members can contact each other using an e-mail form.

The plan is to further develop the interactive facilities of the website. This goal emerged from the working group discussions held during the first Annual Conference of the GSCN, where the partici-pants expressly requested the establishment of an interactive communications platform, which would be of particular benefit to young scientists, with a greater functional capacity to exchange and discuss methods and technical questions. Also envisaged are a jobs portal covering Germany, and informa-tion portals for bachelor- and master-level students who wish to read up on topics such as laboratory placements in the field of stem cell research. The design of content for this and other forums will be suggested by the members (during the work carried out by the working groups) and will be imple-mented in conjunction with the members of the coordination office. Based on member profiles, the coordination office will also create a database of experts from which it will be possible to identify the proper contact for queries relating to media, schools, patient groups and policies. The profiles will be created based on information provided independently by each scientist.

The website for the 1st Annual Conference of the GSCN was launched on July 1, 2013. The online registration of participants and the submission of abstracts was handled using the virtual congress manager “vCongress” supplied by SciSerTec GbR, headquartered at Hanover Medical School (MHH). Respondents to the online survey on the 1st Annual Conference of the GSCN rated the system as very good, giving it 4.29 points out of 5. Please see the separate article ‘The GSCN Annual Conferences’ on page 11 ff. for further results of the online survey and information on the 1st Annual Conference of the GSCN.

Online Elections for the 2013 Board and 1st Members’ Meeting of the GSCNThe 1st Members’ Meeting of the GSCN, which was held in the Max Delbrück Center for Molecular Medicine (MDC) on November 12, in Berlin, took place during the 1st Annual Conference of the GSCN (November 11 – 13, 2013) with 150 of 271 members (55%) attending. The minutes and the presenta-tion on the Members’ Meeting can be downloaded at the members’ portal. The Members’ Meeting was preceded by online elections to the Board, which were conducted from October 1 – 29, 2013 using a certified online voting system supplied by Polyas GmbH. 71 of the 164 members (membership status on September 30, 2013) with voting rights (43%) took part in the online elections. The Designated President for 2014, the Treasurer and three other members were elected to the Extended Board from a pool of candidates previously proposed by the members. After approving the actions of the Exec-utive Board, the following members were welcomed to the Executive and Extended Boards in their new positions: Andreas Trumpp (Acting President and Chair November 2013 – November 2014), Ol-iver Brüstle (Senior President and 1st Vice Chair 2013/14) Thomas Braun (Designated President and 2nd Vice Chair 2013/14), Michael Cross (Treasurer November 2013 – November 2016) in addition to

1st Members’ Meeting of the GSCN on 12 November 2013 in Berlin

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Albrecht Müller, Micha Drukker and Ana Martin-Villalba (Extended Board). Hartmut Geiger (Ulm) and Hannes Klump (Essen) were elected at the Members’ Meeting as annual accounts auditors for the next Members’ Meeting.

Outreach ActivitiesRegular participation in and organization of public events for the general public, schools and jour-nalists should facilitate the efficient transfer of knowledge from research into the public domain. The intention is to contribute towards public opinion while taking into account ethical and legal questions. The GSCN has set itself the target of equally representing all areas of stem cell research. In addition to expertise in the natural sciences and biomedicine, the network also has access to clinical expertise. Fu-ture plans include adding experts from the fields of ethics, law and the social sciences by means of the advisory board and the database of experts. The network thus represents a competent and objective point of contact for politics, the media, commerce, patients and other stakeholders.

In 2013, Daniel Besser represented the network at 4 public events and 9 national and international scientific meetings.

GSCN information booth and stem cell game from EuroStemCell at the 60 Years of DNA event for teachers and students

Public Events:

• The Long Night of Science, June 8, 2013 in Berlin

• 60 Years of DNA, September 13 – 14, 2013 in Berlin

• Capital forum MINT 400 of MINT-EC, November 28, 2013 in Berlin

• Series of advanced education for teach-ers and students ‘Perspectives in the life sciences’, January 7, 2014 in Berlin

Press Contact

A press conference was held during the Founding Meeting on May 7, 2013, and a press meeting was organized at the 1st GSCN Annual Conference on November 12, 2013. Overall during the reporting period, the GSCN coordination office handled more than 20 direct enquiries from journalists for com-ments on current events and led to more than 20 published items in the press.

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Scientific Events:

• 11th Annual Meeting of the International Society of Stem Cell Research (ISSCR), June 11 - 15, 2013 in Boston

• 8th Annual Meeting of the Society for Stem Cell Re-search [Gesellschaft für Stammzellforschung (GSZ)], September 6 - 7, 2013 in Rostock

• International Meeting of the Section ‘The Didactics of Biology’ [Fachsektion Didaktik der Biologie (FDdB)] in VBio, September 16 - 19, 2013 in Kassel

• Stem Cell Symposium, 30 September – October 1, 2013 in Würzburg

• Herrenhausen Symposium on Stem Cells and Regenerative Medicine, October 8 - 10, 2013 in Hanover

• Conference “Chromatin Dynamics & Stem Cells“, October 17 - 20, 2013 in Mainz

• World Conference on Regenerative Medicine (WCRM), October 23 - 25, 2013 in Leipzig

Daniel Besser and Dorota Kaniowska

During the WRCM 2013, the GSCN awarded a Poster Prize for Basic Stem Cell Research to Dorota Kanio-wska (Translational Centre for Regenerative Medicine (TRM), Regulatory Molecules & Delivery Systems, Leipzig) for the abstract “The therapeutic potential of miRNA 665 and its modulatory effect on osteogenic differentiation of murine embryonic stem cells.”

Activities of the Working GroupsThe working groups determine the content of the topic-specific sessions at the annual conference and in the future they should conduct their own meetings and workshops (e.g. for specific target groups such as young scientists and also jointly with partners from industry), in addition to and independent of the an-nual conference. The goal of the working group structure is to ensure the participation of scientists with quite varied backgrounds and topical interests and also to disseminate the latest research techniques and aims. Scientists at all stages of their careers are called on to cooperate in the working groups to help shape the substance of the work and activities of the GSCN (bottom-up approach). In terms of content, the working groups are divided into scientific and strategic topics.

The members in the scientific working groups will discuss the most recent research activities and in-teract in specific projects. Furthermore, discussions will be initiated to explore how research can ap-proach scientific questions with novel methods.

The strategic working groups should stimulate an effective transfer of knowledge and communication between stem cell research and adjacent fields of research and support a discourse with stakeholders, patient groups and the general public.

The measures below arose in the group discussions of the working group sessions during the 1st Annual Conference of the GSCN:• Development of the website’s interactive facilities, construction of a communication platform• Participation of the GSCN in meetings and conferences of other associations (e.g. German Consortium

of Translational Cancer Research (DKTK), DGTI) and organizations (e.g. ISSCR).• Development of a mentoring and internship program• Organization of specific workshops during the next GSCN annual conference• An additional working group on ‘Hematopoietic stem cells’

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Funding is available to working groups for the organization of scientific meetings (retreats), GSCN satel-lite symposiums for conferences, workshops (including partners from companies), additional activities during the annual conference (particularly to provide advice and continuing professional development measures for young scientists), expert meetings (pharmaceuticals, regulatory processes) and the crea-tion of information materials including editorial activities (white papers, outreach programs, media). The central office manages the distribution of funds under defined criteria, with the help of a selection panel when appropriate.

FinancesThe GSCN is a nonprofit association financed through membership fees and funds from the Federal Min-istry of Education and Research (BMBF). According to Section 4 of the statutes and rules of the GSCN, the level of member fees are regulated in the membership fee provisions passed at the Members’ Meeting. The fees are shown on the application form for membership of the GSCN.

The financial year corresponds to the calendar year. Membership fees are due at the beginning of the financial year. It is the Executive Board’s responsibility to prepare the association’s annual statement of accounts and to submit it to the Members’ Meeting. The financial situation is presented in detail at the Members’ Meetings.

From March 2013 to March 2014, the GSCN was supported by funding amounting to €312,500 granted to the Max Delbrück Center for Molecular Medicine (MDC) by the Federal Ministry of Education and Re-search (BMBF) via the project management VDI Technologiezentrum.

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