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Stem cells

cure not just curiosity

By

Islam Osman 5th year

tem cell is the mother of all cells , it’s a blank unspecialized immature cell that has the

capacity of self-renewal and differentiated cells regeneration .

Unique features:stem cell has some properties that make it different from other cells Self-renewal : stem cells are capable of dividing and renewing themselves for long periodsDifferentiation: stem cells are blank cells that can be transformed to other types of cells.Plasticity: the ability of stem cells from one tissue to generate specialized cell type of another tissue, for example hemopoietic cells may give rise to skeletal, myocardial and hepatic cells.Potency: it’s the differentiation potential of the stem cells and according to potency stem cells can be classified.

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Stem cells by Islam Osman Page 1

Classification of stem cells:stem cells can be calssified according to potency to Totipotent: stem cells produced from fusion of an egg and sperm. Cells produced by the first few divisions of the fertilized egg are also totipotent. These cells can be differentiated into embryonic and extra embryonic cell types (e.g. placenta) Pluripotent: stem cells derived from inner cell mass of the blastocyst and can differentiate into cells derived from any of the three germ layers excluding the placenta.Multipotent: stem cells that can produce only cells of closely related family of cells for example hematopoietic stem cells can differentiate into red blood cells. White blood cells, platelets, etc.. .

Oligopotent: stem cells that

can differentiate to only few cells, for example lymphoid stem cells.Bipotent: dual differentiation, for example oval cells can differentiate into hepatic and biliary epithelium.Unipotent: stem cells that can produce only one cell type …for example muscle stem cells. stem cells could be classified

also According to their origin into:Embryonic stem cells: isolated from the inner cell mass of the blastocyst of the discarded embryos after IVF( in vitro fertilization) or from aborted embryos ,which has an ethical debate in different thoughts and religions as embryos are destroyed when inner cell mass is taken.


Fetal stem cells: obtained from aborted fetal gonadal tissue.Cord blood stem cells: obtained from the remaining blood in the umbilical cord after delivery, these cells contain a big deal of hemopoietic stem cells.Adult stem cells: are multipotent stem cells present in few numbers in many sites(bone marrow and niches) of human body.

Embryonic VS Adult stem cellsEmbryonic stem cells pluripotent i.e. can differentiate to all types of cells. They have unlimited power of self-renewal .and in comparison to adult stem

cells , embryonic stem cells are easier to be obtained (by IVF) or cloning . the main disadvantages of embryonic stem cells is the ethical problem about the way they are obtained and the danger of immune rejection later on . Besides embryonic stem cells can be tumorigenic (develop teratomes) on the other hand, adult stem cells are not tumorigenic or immunogenic and the way we obtain them cause no harm.but they have limited potency and self-renewal capacity.

Are there other sources of stem cells ?the answer was negative till the emergence of the last few years , science have exceeded the classic limit of stem cells knowledge by the appearance of two miracles , induced pluripotent stem cells (IPSc) and stimulus triggered conversion of somatic cells into pluripotency (STAP) .Induced pluripotent stem cells In the year of 2007 , professor Shinya Yamanaka and his


research team said that aduld defferenitated cells can be transformed into pluripotent cells , and they published their results of transforming adult human fibroblasts into pluripotent cells by defined factors. the evidence of success of the trial is the ability of the induced cells to develop tumors (teratoma) which is a sure sign of their pluripotency by the capacity to develop into ectodermal,mesenchymal,endodermal derived structures.

Shinya Yamanaka was given Nobel Prize in physiology for the year 2012 in grateful to


his promising work .

Stimulus –Triggered Acquisition of pluripotency (STAP)the newest breakthrough in the field of stem cell research was declared by the beginning of this year (2014) by the valuable research of Haruko Obokata . simply , adult cells like lymphocytes were exposed to strong external stimulus like transient low PH resulting in plruipotency.


After doing the resarch using lymphoctes , Obokata did it on other cells of the bdoy and the same results were obtained.


Applications of stem cells

the last two decades have witnessed a revolution in stem cells uasge in fighting a lot of disease and many trials to understand many diseases ..here, I will try to give a brief about these applications.

In the field of basic research:clarification of complex events that occur during human development and understanding molecular basis of cancer.molecular mechanisms for gene control. Role of signals in gene expression and defferentiation of stem cells .stem cell theory of cancer.In the field of biothchnology (Drugs):stem cells can provide specific cell types to test new drugs .that will reduce animal testing . also stem cell lines will help in the development of effective anti-tumor drugs.

Cell based therpaies:Regerative therapy for many diseases like Parkinsonism , Alzhimer’s ,spinal cord injury , stroke , burns , heart diseases , diabetes …stem cells In gene therapy .Stem cells in cancer therapy.


Cardio-vascular applications of stem cellsCardiovascular disease (CVD), which includes hypertension, coronary heart disease, stroke, and congestive heart failure, has ranked as the number one cause of death in the United States every year since 1900 except 1918, when the nation struggled with an influenza

epidemic. Nearly 2600 Americans die of CVD each day, roughly one person every 34 seconds. Given the aging of the population and the relatively dramatic recent increases in the prevalence of cardiovascular risk factors such as obesity and type 2 diabetes, CVD will be a significant health concern well into the 21st century.

Cardiovascular disease can deprive heart tissue of oxygen, thereby killing cardiac muscle cells (cardiomyocytes). This loss triggers a cascade of detrimental events, including formation of scar tissue, an overload of blood flow and pressure capacity, the overstretching of viable cardiac cells attempting to sustain cardiac output, leading to heart failure, and eventual death. Restoring damaged heart muscle tissue, through repair or regeneration, is therefore a potentially new strategy to treat heart failure.

The use of embryonic and adult-derived stem cells for cardiac repair is an active area of research. A number of stem cell types, including embryonic stem (ES) cells,


cardiac stem cells that naturally reside within the heart, myoblasts (muscle stem cells), adult bone marrow-derived cells including mesenchymal cells (bone marrow-derived cells that give rise to tissues such as muscle, bone, tendons, ligaments, and adipose tissue), endothelial progenitor cells (cells that give rise to the endothelium, the interior lining of blood vessels), and umbilical cord blood cells, have been investigated as possible sources for regenerating damaged heart tissue. All have been explored in mouse or rat models, and some have been tested in larger animal models, such as pigs.

A few small studies have also been carried out in humans, usually in patients who are undergoing open-heart surgery. Several of these have demonstrated that stem cells that are injected into the circulation or directly into the injured heart tissue appear to improve cardiac function and/or induce the formation of new capillaries. The mechanism for this repair remains controversial, and the stem cells likely regenerate heart tissue through several pathways. However, the stem cell populations that have been tested in these experiments vary widely, as do the conditions of their purification and application. Although much more research is needed to assess the safety and improve the efficacy of this approach, these preliminary clinical experiments show how stem cells may one day be used to repair damaged heart tissue, thereby reducing the burden of cardiovascular disease.


Stem cells in diabetes Milletus

Scientists believe they may have moved a step closer to a cure for the type of diabetes that develops in childhood and usually leads to a lifetime of insulin injections.

Researchers in California report that they have reversed the equivalent of type 1 diabetes in mice through transplants of stem cells. Their experiments have replaced cells in the pancreas damaged by the disease that are unable to make insulin.

Without insulin, the body has difficulty absorbing sugars such as glucose from the blood. The disease usually first shows in childhood or

early adulthood and used to be a killer, but glucose levels can now be monitored and regulated with insulin injections.

Scientists have long wanted to try to replace the damaged ß-cells that normally produce insulin. This has been one of the prime targets of stem cell experiments. But until now, it has proved difficult, partly because mature ß-cells do not readily regenerate.

Writing in the journal Cell Stem Cell, scientists at the Gladstone Institutes in San Francisco describe how they took a step back and collected skin cells, called fibroblasts, from laboratory mice. Then, by treating the fibroblasts with a unique "cocktail" of molecules and reprogramming factors, they transformed the cells into endoderm-like cells. Endoderm cells are a type of cell found in the early embryo, and which eventually mature into the body's major organs – including the pancreas. "Using another chemical cocktail, we then transformed these endoderm-like cells into cells that mimicked early pancreas-like


cells, which we called PPLCs," said the Gladstone postdoctoral scholar Ke Li, the paper's lead author. "Our initial goal was to see whether we could coax these PPLCs to mature into cells that, like ß-cells, respond to the correct chemical signals and – most importantly – secrete insulin. And our initial experiments, performed in a petri dish, revealed that they did."

The team then injected these cells into mice that had been genetically modified to have high glucose levels, mimicking the type 1 diabetes condition in humans.

"Importantly, just one week post-transplant, the animals' glucose levels started to decrease, gradually approaching normal levels," said Li. "And when we removed the transplanted cells, we saw an immediate glucose spike, revealing a direct link between the transplantation of the PPLCs and reduced hyperglycemia [high glucose level]."

Eight weeks after the transplantation, the scientists

found that the pancreas-like cells had turned into the real thing – fully functional insulin-secreting ß-cells had developed in the mice.

The team says this is proof of principle, which one day might be used to cure type 1 diabetes in humans. "I am particularly excited about the prospect of translating these findings to the human system," said Matthias Hebrok, one of the study's authors and director of the UCSF Diabetes Center. "Most immediately, this technology in human cells could significantly advance our understanding of how inherent defects in ß-cells result in diabetes, bringing us notably closer to a much-needed cure.

Stem cells in skin burnsStem cells may have a promising role in the treatment of extenxive burns and lrge ulcer through providing suffiecent numbers of epidermal and epithelial cell lines that can be used in replacing damged tissues.


Ethical debate about stem cellsEmbryoinc stem cells are derived from the balstocyst which become distroyed after aspiration of the inner cell mass.though many question appear logically..Is an embyro a person?Is it morally accepted to use embryos for reaserch ?Is that considered murder?

some people are in favour of the stem cell and they have their own motives …embryoinc stem cells will decrease human suffering and get rid off a lot of diseases that hinder human production ..that is a global human aim .embryonic stem cells are taken from excess IVF that will be discarede anyway ..so it’s better to use them.

the other face of the debate is against stem cells research entirely and speciallly against embryonic stem cells ..also they have their own thoughts about that..

taking the cells from the balstocyst destroys it ..that’s murder..embryonic stem cells research will open the door to reproductive cloning ..and that will replace the role of God ..

the emergence of the great discovery of Shinya Yamanaka and the STAP technique will put an end for this debate for sure ..there will no need to destroy embryos anymore ..as adult own cells will be transformed into pluripotency by usage of some transcription genes or some stressor factors.

also the religin and politics play an important role in directioning stem cell research all over the world..


References :

1-Robert Lanza , Essentials of stem cells , second edition.2-Stewart Sell , Stem Cells Handbook .3- Takahashi, Kazutoshi; Yamanaka, Shinya (2006). "Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors". Cell 126 (4): 663–6764- Obokata, Haruko; et al. (2014-01-30). "Stimulus-triggered fate conversion of somatic cells into pluripotency". Nature 505 (7485): 641–647.5- Jain, KK (2002). "Ethical and regulatory aspects of embryonic stem cell research". Expert opinion on biological therapy 2 (8): 819–266- Current Regulation of Human Embryonic Stem Cell Research (2005). Guidelines for Human Embryonic Stem Cell Research. Washington D.C, The National Academies Press: 63-807- http://en.wikipedia.org/wiki/Main_Page


http://www.nature.com/nature/journal/v505/n7485/abs/nature12968.html

http://www.nature.com/nature/journal/v505/n7485/abs/nature12968.html