Human embryonic stem cells: preclinical perspectives

Deb, Kaushik; Sarda, Kanchan

doi:10.1186/1479-5876-6-7

Cited by 35 publications

(23 citation statements)

References 81 publications

(72 reference statements)

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“…Such cells when injected into immunocompromised hosts are believed to form teratomas. At present, this property of ES cells is a major limitation to their clinical utility (23). We wondered whether in contrast to our observations regarding differentiation, a reciprocal relationship existed between membrane potential and teratoma formation.…”

Section: Resultsmentioning

confidence: 63%

Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells

Schieke

Cao

et al. 2008

Journal of Biological Chemistry

172

140

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Relatively little is known regarding the role of mitochondrial metabolism in stem cell biology. Here we demonstrate that mouse embryonic stem cells sorted for low and high resting mitochondrial membrane potential (⌬⌿ m L and ⌬⌿ m H) are indistinguishable morphologically and by the expression of pluripotency markers, whereas markedly differing in metabolic rates. Interestingly, ⌬⌿ m L cells are highly efficient at in vitro mesodermal differentiation yet fail to efficiently form teratomas in vivo, whereas ⌬⌿ m H cells behave in the opposite fashion. We further demonstrate that ⌬⌿ m reflects the degree of overall mammalian target of rapamycin (mTOR) activation and that the mTOR inhibitor rapamycin reduces metabolic rate, augments differentiation, and inhibits tumor formation of the mouse embryonic stem cells with a high metabolic rate. Taken together, our results suggest a coupling between intrinsic metabolic parameters and stem cell fate that might form a basis for novel enrichment strategies and therapeutic options.Stem cells persist throughout the entire life span of the organism, suggesting that these cells may possess unique abilities to deal with issues such as oxidative stress and DNA damage. Such supposition is supported by experimental evidence that murine embryonic stem cells (mES) 4 cells appear resistant to exogenous oxidative stress (1). This resistance has been attributed to increased antioxidant protein defenses in mES cells when compared with more differentiated mouse cells (1). There is also evidence that stem cells may preferentially reside in low oxygen niches (2). The best studied example appears to be for hematopoietic stem cells where both theoretical and direct experimental evidence suggests that hematopoietic stem cells preferentially reside within the most hypoxic regions of the bone marrow (3, 4). It has long been known that lowering ambient oxygen concentrations can regulate mitochondrial metabolism and hence alter intracellular reactive oxygen species generation (5). In this context, it is believed that residing within low oxygen environments may help reduce the long term exposure of the stem cell to oxidative damage.Consistent with a role for ambient oxygen in determining stem cell fate, a number of reports have previously demonstrated that low levels of oxygen might promote hematopoietic stem cell function (6 -8). Similarly, it has been demonstrated that the differentiation of mES cells into hematopoietic progenitors was augmented under hypoxic conditions (9). Such observations are not, however, limited to hematopoietic differentiation as oxygen concentration appears to also affect the differentiation of neural stem cells (10, 11), as well as placental cytotrophoblast cells (12).The precise molecular bases for these effects are unclear. Several studies have implicated that activation of hypoxia-inducible factor 1␣ (HIF-1␣) or HIF-2␣ may play a significant role in the observed enhanced differentiation of stem cells under low oxygen conditions (2). Such observations are supported by st...

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Section: Resultsmentioning

confidence: 63%

Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells

Schieke

Cao

et al. 2008

Journal of Biological Chemistry

172

140

View full text Add to dashboard Cite

show abstract

“…Nevertheless, ESCs present several problems for cell transplant therapy (Deb and Sarda, 2008;Daley and Scadden, 2008, for reviews). First is the possibility of contamination of the ESCs from mouse feeder layers or animal serum-supplemented medium with pathogens or xenogens (cells or proteins) that might trigger host immune reactions.…”

Section: Issues Surrounding the Use Of Ascs And Escs For Cellbased Thmentioning

confidence: 99%

Stretching the limits: Stem cells in regeneration science

Stocum

Zupanc

2008

Developmental Dynamics

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“…Note-se que estes três genes, isolados ou em associação entre eles, são responsáveis pela expressão de mais de 2.000 outros genes envolvidos nos processos de autorrenovação e de manutenção da plasticidade e pluripotência das células-tronco. 66 O fenótipo de amniócitos mesenquimais humanos expandidos em cultura é similar ao relatado para células-tronco mesenquimais derivadas de tecido fetal do segundo trimestre de gestação e medula óssea de adulto. As AF-MSCs humanas podem diferenciar-se em uma ampla gama de células.…”

Section: Diferenciação Das Células-tronco Mesenquimais Do Líquido Amnunclassified

Células-tronco do líquido amniótico

Bydlowski¹,

Debes²,

Duarte³

et al. 2009

Rev. Bras. Hematol. Hemoter.

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Células-tronco do líquido amniótico Amniotic fluid stem cells IntroduçãoO fluido amniótico humano tem sido utilizado no diagnóstico pré-natal já há mais de 70 anos. O primeiro relato sobre amniocentese foi em 1930, no qual os autores tentaram correlacionar o número de células presentes no líquido amniótico e o fenótipo celular com o sexo e a saúde do feto. Atualmente, uma das principais utilizações diagnósticas do líquido amniótico é no isolamento de células fetais para cariotipagem, no exame de anormalidades cromossômicas. Recentemente, foram apresentadas evidências de que o lí-quido amniótico pode ter outras aplicações, além da utilização como ferramenta diagnóstica. Ele pode ser importante fonte de células terapêuticas para vários distúrbios, tanto congênitos quanto no adulto.O líquido amniótico contém uma quantidade muito grande de células em suspensão, população celular que é variá-vel com a fase da gestação e que traduz as mudanças na formação do líquido amniótico e da maturação fetal e de seus anexos.

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Human embryonic stem cells: preclinical perspectives

Cited by 35 publications

References 81 publications

Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells

Mitochondrial Metabolism Modulates Differentiation and Teratoma Formation Capacity in Mouse Embryonic Stem Cells

Stretching the limits: Stem cells in regeneration science

Células-tronco do líquido amniótico

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