Editorial Hematopoietic and Mesenchymal Stem Cells in...

EditorialHematopoietic and Mesenchymal Stem Cells in Biomedical andClinical Applications

Albert A Rizvanov1 Jenny Persson2 Fikrettin Fahin3

Saverio Bellusci4 and Paulo J Oliveira5

1 Institute of Fundamental Medicine and Biology Kazan Federal University Kazan Russia2Division of Experimental Cancer Research Department of Laboratory Medicine Lund University Malmo Sweden3Department of Genetics and Bioengineering TC Yeditepe Universitesi Istanbul Turkey4Excellence Cluster Cardio-Pulmonary System Justus Liebig University Giessen Germany5CNC-Center for Neuroscience and Cell Biology UC Biotech Building University of Coimbra Cantanhede Portugal

Correspondence should be addressed to Albert A Rizvanov albertrizvanovkpfuru

Received 1 November 2016 Accepted 3 November 2016

Copyright copy 2016 Albert A Rizvanov et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited

Stem cell-based therapy is emerging as a major area ofinvestigation not only to understand the basic signalingmechanisms that regulate cell fate but also to involve themas a novel approach for the treatment of multiple humandiseases The interest in stem cells is growing each yearStem cell research is transversal to many fields of researchranging from embryology to reproduction to cell division tocell differentiation to therapies and even to plant biologyIt is thus not surprising that the stem cell field is gainingmore and more relevance and maturity despite some majordisappointments [1]

Despite advances in biomedical and clinical researchmany diseases and conditions have no known cure or still donot have adequate therapies which would result in sufficientrecovery and high quality of life for patients Boosting thenatural regenerative abilities of the human body seems like apromising therapeutic strategy Stem cells possess an abilityfor self-renewal and differentiation into several cell typesthus playing an important role in natural replacement ofaged or apoptotic cells as well as regeneration of damagedtissues Mesenchymal and hematopoietic stem cells play animportant role in many regeneration processes in the humanbody Moreover according to recent studies mesenchymaland hematopoietic stem cells form a unique bone marrowniche [2] Not surprisingly hematopoietic and mesenchymal

stem cells are considered to be themost promising adult stemcell types for developing cell- or gene-based therapies

The present special issue deals with the biomedical andclinical applications of hematopoietic andmesenchymal stemcells serving as a pit stop for many stem cell researchers notonly to review the latest literature but to improve their currentknowledge onmesenchymal (MSCs) and hematopoietic stemcells (HSCs)

Mesenchymal stem cells are a promising source of stemcells for regenerativehealing therapy as illustrated by severalinteresting papers present in the current edition MSCs aredistinct from the hematopoietic stem cells and have thecapacity to differentiate into multiple cell types includingadipocytes chondrocytes myocytes and osteoblasts MSCsdo not give rise to differentiated cells in the hematopoieticlineage

The study by H Zhao et al reports the therapeutic effectsof MSC on Severe Acute Pancreatitis (SAP) in rats Theauthors elegantly show that MSC transplantation improvesthe prognosis of SAP Engrafted MSCs have the capacity ofhoming migrating and establishment during the treatmentof SAP

The study by C Yin et al investigated the role of umbilicalcord-derivedmesenchymal stem cells (UC-MSCs) in regulat-ing angiogenesis and relieving hindlimb ischemia They suc-cessfully demonstrated that the isolated UC-MSCs notably

Hindawi Publishing CorporationStem Cells InternationalVolume 2016 Article ID 3157365 3 pageshttpdxdoiorg10115520163157365

2 Stem Cells International

contributed to restoring blood supply and alleviating thesymptoms of limb ischemia through enhancing angiogenesisopening the way for a novel approach to treat that condition

The review by A J Peired et al summarizes the clinicalevidence for the use of exogenous MSCs to prevent renalinjury and promote renal recovery Ongoing clinical trials areexpected to provide further insight into safety feasibility andefficacy of MSC-based therapy in renal pathologies and allowthe design of consensus protocol for clinical purpose

The review by S Li et al summarizes the current statustherapeutic potential and the detailed factors ofMSCs-basedtherapeutics for ischemic cerebrovascular disease ischemiccardiomyopathy and diabetic foot Diabetes and its relatedcomplications are in fact a large cause of morbidity andmortality nowadays in theWestern countries mostly derivedfrom incorrect lifestyles

The review by Q Wu et al explores further the rolesand functional mechanisms of MSCs in diabetic foot diseaseInsights into current and future studies are presented

Related to the previous topic the review by K Mat-sushita discusses the current understanding of the rela-tionship between MSCs and metabolic syndrome (obesitydyslipidemia and diabetes) The author also discusses theirpotential implications in diseasemanagement presenting alsothe pitfalls associated with their use

Each organ has potentially a source of mesenchymal stemcell called resident mesenchymal stem cells Placenta cordblood and amniotic fluid at birth as well as adipose tissue orthe dental pulp of baby teeth postnatally have been shown tobe a practical easily accessible source of MSCs

The study fromH Ren et al compares the biological char-acteristics including morphology proliferation antiapopto-sis multilineage differentiation capacity and immunopheno-type of umbilical cord dental pulp and menstrual blood-MSCs in order to provide a theoretical basis for the clinicalselection and application of these cells Their results suggestthat dental pulp-MSCs collected in an easy and noninvasiveway may be a desired source for clinical applications of celltherapy

Another emerging area of research is the manipulation ofMSCs in vitro before in vivo transplantation to enhance theirregenerativehealing capabilitiesThree studies in the presentspecial edition deal with this important research question

The study by P Muller et al focuses on CD133+ stem cellswhich are very promising for regenerative medicine Usingmagnetic polyplexes carrying microRNA they specificallytargeted human CD133+ stem cells without altering theirstem cell potential The approach described in this work maybe used for a better selection of cells in order to enhance theirtherapeutic effects

Another study by L Jinfeng et al is based on the premisesthat appropriate gene transduction before transplantation ofMSCs derived from the human umbilical cord is a promisingprocedure for cell therapy Fibroblast Growth Factor-20(FGF-20) has been reported to protect dopaminergic neuronsagainst a range of toxic insults in vitro In this paper MSCswere gene transduced with FGF-20 and transplanted intoa mice model of Parkinsonrsquos disease The authors reportedthat transduced MSCs have the potential for improving

Parkinsonrsquos disease closely related to the degradation of NF-120581B a transcription factor that controls genes encoding proin-flammatory cytokines highly expressed in the nigrostriataldopaminergic regions in Parkinsonrsquos disease patients

The study by D Ye et al investigated whether theDNA methyltransferase inhibitor (DNMTi) 5-aza-21015840-deoxy-cytidine and the histone deacetylase inhibitor (HDACi)trichostatin A regulated hepatic differentiation of rat bonemarrow-derived mesenchymal stem cells (rBM-MSCs) aswell as their therapeutic effect on liver damage The authorsshowed that HDACis enhanced hepatic differentiation in atime-dependent manner while DNMTis did not induce thehepatic differentiation of rBM-MSCs in vitro

How endogenousMSCs can be recruited to the site of injuryis another key aspect in MSC research with very importantimplications in tissue regeneration

The study by E Muinos-Lopez et al evaluated the effectof intra-articular or a combination of intra-articular andintraosseous infiltration of Platelet-Rich Plasma (PRP) onthe cellular content of synovial fluid (SF) of osteoarthriticpatients The authors demonstrated that the synovial fluid ofosteoarthritic patients contains a population of MSCs thatcan be modulated by Platelet-Rich Plasma infiltration of thesubchondral bone compartment

MSCs cells can either act as a source of differentiated cellsorandmodulate the local inflammatory status via the secretionof cytokines possibly highlighting their potential therapeuticrole in immune diseases MSCs have been used so far inclinical trials for osteoarthritis autoimmune disease (Crohnrsquosdisease multipole sclerosis systemic lupus erythematosusand systemic sclerosis) or systemic diseases such as graft-versus-host diseases and sepsis

The study by M A Al Jumah et al characterized the roleofmesenchymal stemmultipotent stromal cells fromdeciduabasalis of human term placenta-derived mesenchymal stemcells (DBMSCs) They showed that DBMSCs differentiateinto threemesenchymal lineages (adipocytes osteocytes andchondrocytes) DBMSCs express and secrete a distinct com-bination of cytokines growth factors and immunemoleculesthat reflect their unique microenvironment The authorssuggested that DBMSCs could be attractive alternative can-didates forMSC-based therapies that treat diseases associatedwith inflammation and oxidative stress

The review by B Sangiorgi and R A Panepucci is focusedon the immunomodulatory properties of mesenchymal stro-mal cells (MSCs) in regard to their potential use in thetreatment of graft-versus-host disease In their review theauthors illustrate how Pathogen-associated molecular pat-terns modulate the immunosuppressive phenotype of humanMSCs by signaling through toll-like receptors

Hematopoietic stem cells are among the first stem celltypes used in the clinic mainly to treat blood disordersand restore hematopoietic function after radiation andchemotherapy Besides their natural ability to differentiateinto multiple hematopoietic lineages these cells are alsoconsidered for therapy of many other diseases such as neu-rodegenerative diseases autoimmune diseases and differenttypes of traumatic injuries Finally some types of cancerstem cells are thought to originate from hematopoietic stem

Stem Cells International 3

cells It is therefore crucial to understand the molecularand cellular bases controlling the survival proliferationand differentiation of these cells in order to develop newtherapeutic strategies for oncology

The study by Y-C Liu et al is focused on investigating theprognostic factors that may predict patient outcome after theallogeneic hematopoietic stem cell transplantation (HSCT)It is important to identify new prognostic factors that maypredict graft-versus-host disease and relapse-free survivals

The study by J Li et al showed that the intraperi-toneally transplanted multiplacentas pooled cells can surviveand engraft into the host body through blood circulationThe aplastic anemia model mice which received the mul-tiplacentas pooled cells display increased peripheral bloodhemoglobin level In turn increased hemoglobin is thoughtto be causative for the observed increased life span of aplasticanemia model mice after intraperitoneal transplantation ofthese cells

The review by P Sontakke et al overviewed the mousexenograft models that have been used for studying themolecular pathology of Chronic Myeloid Leukemia (CML)The authors also described the advantages of using themouse models of CML to develop and improve therapeuticapproaches for this disease Interestingly the authors pro-posed that the stem cell technologies which are applied in theestablishment of animalmodels canmaintain patient tumor-derived CML-subclones that are genetically identical to thosein patients

Albert A RizvanovJenny PerssonFikrettin SahinSaverio BellusciPaulo J Oliveira

References

[1] D Lukovic M Stojkovic V Moreno-Manzano S S Bhat-tacharya and S Erceg ldquoPerspectives and future directionsof human pluripotent stem cell-based therapies lessons fromGeronrsquos clinical trial for spinal cord injuryrdquo Stem Cells andDevelopment vol 23 no 1 pp 1ndash4 2014

[2] S Mendez-Ferrer T V Michurina F Ferraro et al ldquoMesenchy-mal and haematopoietic stem cells form a unique bone marrownicherdquo Nature vol 466 no 7308 pp 829ndash834 2010

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2 Stem Cells International

contributed to restoring blood supply and alleviating thesymptoms of limb ischemia through enhancing angiogenesisopening the way for a novel approach to treat that condition

The review by A J Peired et al summarizes the clinicalevidence for the use of exogenous MSCs to prevent renalinjury and promote renal recovery Ongoing clinical trials areexpected to provide further insight into safety feasibility andefficacy of MSC-based therapy in renal pathologies and allowthe design of consensus protocol for clinical purpose

The review by S Li et al summarizes the current statustherapeutic potential and the detailed factors ofMSCs-basedtherapeutics for ischemic cerebrovascular disease ischemiccardiomyopathy and diabetic foot Diabetes and its relatedcomplications are in fact a large cause of morbidity andmortality nowadays in theWestern countries mostly derivedfrom incorrect lifestyles

The review by Q Wu et al explores further the rolesand functional mechanisms of MSCs in diabetic foot diseaseInsights into current and future studies are presented

Related to the previous topic the review by K Mat-sushita discusses the current understanding of the rela-tionship between MSCs and metabolic syndrome (obesitydyslipidemia and diabetes) The author also discusses theirpotential implications in diseasemanagement presenting alsothe pitfalls associated with their use

Each organ has potentially a source of mesenchymal stemcell called resident mesenchymal stem cells Placenta cordblood and amniotic fluid at birth as well as adipose tissue orthe dental pulp of baby teeth postnatally have been shown tobe a practical easily accessible source of MSCs

The study fromH Ren et al compares the biological char-acteristics including morphology proliferation antiapopto-sis multilineage differentiation capacity and immunopheno-type of umbilical cord dental pulp and menstrual blood-MSCs in order to provide a theoretical basis for the clinicalselection and application of these cells Their results suggestthat dental pulp-MSCs collected in an easy and noninvasiveway may be a desired source for clinical applications of celltherapy

Another emerging area of research is the manipulation ofMSCs in vitro before in vivo transplantation to enhance theirregenerativehealing capabilitiesThree studies in the presentspecial edition deal with this important research question

The study by P Muller et al focuses on CD133+ stem cellswhich are very promising for regenerative medicine Usingmagnetic polyplexes carrying microRNA they specificallytargeted human CD133+ stem cells without altering theirstem cell potential The approach described in this work maybe used for a better selection of cells in order to enhance theirtherapeutic effects

Another study by L Jinfeng et al is based on the premisesthat appropriate gene transduction before transplantation ofMSCs derived from the human umbilical cord is a promisingprocedure for cell therapy Fibroblast Growth Factor-20(FGF-20) has been reported to protect dopaminergic neuronsagainst a range of toxic insults in vitro In this paper MSCswere gene transduced with FGF-20 and transplanted intoa mice model of Parkinsonrsquos disease The authors reportedthat transduced MSCs have the potential for improving

Parkinsonrsquos disease closely related to the degradation of NF-120581B a transcription factor that controls genes encoding proin-flammatory cytokines highly expressed in the nigrostriataldopaminergic regions in Parkinsonrsquos disease patients

The study by D Ye et al investigated whether theDNA methyltransferase inhibitor (DNMTi) 5-aza-21015840-deoxy-cytidine and the histone deacetylase inhibitor (HDACi)trichostatin A regulated hepatic differentiation of rat bonemarrow-derived mesenchymal stem cells (rBM-MSCs) aswell as their therapeutic effect on liver damage The authorsshowed that HDACis enhanced hepatic differentiation in atime-dependent manner while DNMTis did not induce thehepatic differentiation of rBM-MSCs in vitro

How endogenousMSCs can be recruited to the site of injuryis another key aspect in MSC research with very importantimplications in tissue regeneration

The study by E Muinos-Lopez et al evaluated the effectof intra-articular or a combination of intra-articular andintraosseous infiltration of Platelet-Rich Plasma (PRP) onthe cellular content of synovial fluid (SF) of osteoarthriticpatients The authors demonstrated that the synovial fluid ofosteoarthritic patients contains a population of MSCs thatcan be modulated by Platelet-Rich Plasma infiltration of thesubchondral bone compartment

MSCs cells can either act as a source of differentiated cellsorandmodulate the local inflammatory status via the secretionof cytokines possibly highlighting their potential therapeuticrole in immune diseases MSCs have been used so far inclinical trials for osteoarthritis autoimmune disease (Crohnrsquosdisease multipole sclerosis systemic lupus erythematosusand systemic sclerosis) or systemic diseases such as graft-versus-host diseases and sepsis

The study by M A Al Jumah et al characterized the roleofmesenchymal stemmultipotent stromal cells fromdeciduabasalis of human term placenta-derived mesenchymal stemcells (DBMSCs) They showed that DBMSCs differentiateinto threemesenchymal lineages (adipocytes osteocytes andchondrocytes) DBMSCs express and secrete a distinct com-bination of cytokines growth factors and immunemoleculesthat reflect their unique microenvironment The authorssuggested that DBMSCs could be attractive alternative can-didates forMSC-based therapies that treat diseases associatedwith inflammation and oxidative stress

The review by B Sangiorgi and R A Panepucci is focusedon the immunomodulatory properties of mesenchymal stro-mal cells (MSCs) in regard to their potential use in thetreatment of graft-versus-host disease In their review theauthors illustrate how Pathogen-associated molecular pat-terns modulate the immunosuppressive phenotype of humanMSCs by signaling through toll-like receptors

Hematopoietic stem cells are among the first stem celltypes used in the clinic mainly to treat blood disordersand restore hematopoietic function after radiation andchemotherapy Besides their natural ability to differentiateinto multiple hematopoietic lineages these cells are alsoconsidered for therapy of many other diseases such as neu-rodegenerative diseases autoimmune diseases and differenttypes of traumatic injuries Finally some types of cancerstem cells are thought to originate from hematopoietic stem







References










Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology







References










Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology








Volume 2014

Zoology






















Advances in

Virolog y



Volume 2014




Enzyme Research



Microbiology

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