Human mesenchymal stem cells: from basic biology to clinical applications

Abdallah, Basem M.; Kassem, Moustapha

doi:10.1038/sj.gt.3303067

Cited by 338 publications

(252 citation statements)

References 98 publications

(106 reference statements)

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“…MSC markers include a complete battery of specific CD markers, the ability to differentiate into a limited number of tissues, maintenance of normal karyotype, and transcriptome profiling to identify gene constructs with ''stemness'' characteristics. Additionally, Abdallah and Kassem [2008] postulated that the ''gold standard'' assay for MSC stemness must be based on the ability of these cells to form ectopic bone and bone marrow microenvironments that support hematopoiesis upon implantation in an open system (subcutaneous transplantation) in severely combined immunodeficient (SCID) mice. Several properties common to stem cells of embryonic or adult origin have been shown through transcriptome profiling.…”

Section: What Is the True Definition Of A Bona Fide Stem Cell?mentioning

confidence: 99%

Taking stem cells to the clinic: Major challenges

Bongso

Fong

Gauthaman

2008

J of Cellular Biochemistry

164

111

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Stem cell therapy offers tremendous promise in the treatment of many incurable diseases. A variety of stem cell types are being studied but human embryonic stem cells (hESCs) appear to be the most versatile as they are pluripotent and can theoretically differentiate into all the tissues of the human body via the three primordial germ layers and the male and female germ lines. Currently, hESCs have been successfully converted in vitro into functional insulin secreting islets, cardiomyocytes, and neuronal cells and transfer of such cells into diabetic, ischaemic, and parkinsonian animal models respectively have shown successful engraftment. However, hESC-derived tissue application in the human is fraught with the problems of ethics, immunorejection, tumorigenesis from rogue undifferentiated hESCs, and inadequate cell numbers because of long population doubling times in hESCs. Human mesenchymal stem cells (hMSC) though not tumorigenic, also have their limitations of multipotency, immunorejection, and are currently confined to autologous transplantation with the genuine benefits in allogeneic settings not conclusively shown in large controlled human trials. Human Wharton's jelly stem cells (WJSC) from the umbilical cord matrix which are of epiblast origin and containing both hESC and hMSC markers appear to be less troublesome in not being an ethically controversial source, widely multipotent, not tumorigenic, maintain ''stemness'' for several serial passages and because of short population doubling time can be scaled up in large numbers. This report describes in detail the hurdles all these stem cell types have to overcome before stem cell-based therapy becomes a genuine reality.

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Section: What Is the True Definition Of A Bona Fide Stem Cell?mentioning

confidence: 99%

Taking stem cells to the clinic: Major challenges

Bongso

Fong

Gauthaman

2008

J of Cellular Biochemistry

164

111

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“…I t is envisioned that stem cells, after differentiation to a specific cell lineage, can be employed to treat a large number of musculoskeletal diseases, including bone and cartilage diseases (eg, localized bone and cartilage defects, nonhealing fractures, and systemic age-related degenerative conditions such as osteoporosis and osteoarthritis) (1) and diseases in skeletal muscle and myocardium (eg, muscle dystrophies, myocardial injury following ischemia, and cardiomyopathies). (2) Several adult (tissue-specific) stem cells appear to be suitable for clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

Mahmood

Harkness²,

Schrøder

et al. 2010

Journal of Bone and Mineral Research

119

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Directing differentiation of human embryonic stem cells (hESCs) into specific cell types using an easy and reproducible protocol is a prerequisite for the clinical use of hESCs in regenerative-medicine procedures. Here, we report a protocol for directing the differentiation of hESCs into mesenchymal progenitor cells. We demonstrate that inhibition of transforming growth factor b (TGF-b)/activin/nodal signaling during embryoid body (EB) formation using SB-431542 (SB) in serum-free medium markedly upregulated paraxial mesodermal markers (TBX6, TBX5) and several myogenic developmental markers, including early myogenic transcriptional factors (Myf5, Pax7), as well as myocyte-committed markers [NCAM, CD34, desmin, MHC (fast), a-smooth muscle actin, Nkx2.5, cTNT]. Continuous inhibition of TGF-b signaling in EB outgrowth cultures (SB-OG) enriched for myocyte progenitor cells; markers were PAX7 þ (25%), MYOD1 þ (52%), and NCAM þ (CD56) (73%). DNA microarray analysis revealed differential upregulation of 117 genes (>2-fold compared with control cells) annotated to myogenic development and function. Moreover, these cells showed the ability to contract (80% of the population) and formed myofibers when implanted intramuscularly in vivo. Interestingly, SB-OG cells cultured in 10% fetal bovine serum (FBS) developed into a homogeneous population of mesenchymal progenitors that expressed CD markers characteristic of mesenchymal stem cells (MSCs): CD44 þ (100%), CD73 þ (98%), CD146 þ (96%), and CD166 þ (88%) with the ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro and in vivo. Furthermore, microarray analysis of these cells revealed downregulation of genes related to myogenesis: MYH3 (À167.9-fold), ACTA1 (À161-fold), MYBPH (À139-fold), ACTC (À100.3-fold), MYH8 (À45.5-fold), and MYOT (À41.8-fold) and marked upregulation of genes related to mesoderm-derived cell lineages. In conclusion, our data provides a simple and versatile protocol for directing the differentiation of hESCs into a myogenic lineage and then further into mesenchymal progenitors by blocking the TGF-b signaling pathway. ß

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“…Vários estudos posteriores relataram a multipotência dessas células, ou seja, a capacidade de diferenciarem-se em osteoblastos, condroblastos e adipócitos. (ABDALLAH, et al, 2008).…”

Section: Introductionunclassified

Revisao dos dados citogeneticos em especies da família Hylidae (amphibia, anura): resultados e perspectivas

Catroli¹,

Kasahara²

2009

Publ. Biologicas

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Recebido para publicação em 12/12/2008Aceito para publicação em 07/03/2009 RESUMO Células-tronco são caracterizadas por seu estado indiferenciado e seu alto poder de autorrenovação através de divisões assimétricas. Sob a infl uência de determinados sinais biológicos, elas podem se diferenciar em células fenotipicamente distintas de seus precursores. São divididas em dois grandes grupos de acordo com o local de seu isolamento: embrionárias, que são as células retiradas da camada celular interna do blastocisto; e adultas, que são aquelas encontradas em diversos locais de tecidos pós-natais. As células-tronco mesenquimais, por sua vez, formam um grupo heterogêneo de células adultas multipotentes, capazes de originar tecidos mesenquimais: ósseo, adiposo e cartilaginoso, sendo encontradas tanto em tecidos fetais quanto em adultos. O líquido amniótico humano, um fl uido complexo e dinâmico que envolve o feto durante a gestação, contém uma variedade de célu-las esfoliadas do embrião em sua composição. Procedimentos bem estabelecidos de isolamento, crescimento e expansão das células do líquido amniótico podem proporcionar uma fonte alternativa de células-tronco mesenquimais com diversas aplicações biomédicas.Palavras-Chaves: Células-tronco mesenquimais. Líquido amniótico. Terapia celular. ABSTRACTStem cells are characterized by their undifferentiated state and their high capacity of self renewal through asymmetric divisions. Under the infl uence of certain biological signals they can differentiate into specialized cells phenotypically different from their precursors. They are divided into to their place of origin: embryonic

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Human mesenchymal stem cells: from basic biology to clinical applications

Cited by 338 publications

References 98 publications

Taking stem cells to the clinic: Major challenges

Taking stem cells to the clinic: Major challenges

Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-β/activin/nodal signaling using SB-431542

Revisao dos dados citogeneticos em especies da família Hylidae (amphibia, anura): resultados e perspectivas

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