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Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis

Estrada, J C ; Albo, C ; Benguría, A ; Dopazo, A ; López-Romero, P ; Carrera-Quintanar, L ; Roche, E ; Clemente, E P ; Enríquez, J A ; Bernad, A ; Samper, E

Cell death and differentiation, 2012-05, Vol.19 (5), p.743-755 [Periódico revisado por pares]

England: Nature Publishing Group

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Título:
Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis
Autor: Estrada, J C ; Albo, C ; Benguría, A ; Dopazo, A ; López-Romero, P ; Carrera-Quintanar, L ; Roche, E ; Clemente, E P ; Enríquez, J A ; Bernad, A ; Samper, E
Assuntos: Aneuploidy ; Bioenergetics ; Cell culture ; Cell Culture Techniques - methods ; Cells, Cultured ; Chromosomal Instability - genetics ; Chromosome aberrations ; Data processing ; DNA damage ; Gene expression ; Glycolysis ; Glycolysis - physiology ; Humans ; Life span ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - metabolism ; Mesenchyme ; Original Paper ; Oxidative Phosphorylation ; Oxidative stress ; Oxidative Stress - genetics ; Oxygen - metabolism ; Oxygen tension ; Stem cells ; Telomere - genetics ; Telomeres
É parte de: Cell death and differentiation, 2012-05, Vol.19 (5), p.743-755
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Descrição: Expansion of human stem cells before cell therapy is typically performed at 20% O(2). Growth in these pro-oxidative conditions can lead to oxidative stress and genetic instability. Here, we demonstrate that culture of human mesenchymal stem cells at lower, physiological O(2) concentrations significantly increases lifespan, limiting oxidative stress, DNA damage, telomere shortening and chromosomal aberrations. Our gene expression and bioenergetic data strongly suggest that growth at reduced oxygen tensions favors a natural metabolic state of increased glycolysis and reduced oxidative phosphorylation. We propose that this balance is disturbed at 20% O(2), resulting in abnormally increased levels of oxidative stress. These observations indicate that bioenergetic pathways are intertwined with the control of lifespan and decisively influence the genetic stability of human primary stem cells. We conclude that stem cells for human therapy should be grown under low oxygen conditions to increase biosafety.
Editor: England: Nature Publishing Group
Idioma: Inglês

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Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis

Estrada, J C ; Albo, C ; Benguría, A ; Dopazo, A ; López-Romero, P ; Carrera-Quintanar, L ; Roche, E ; Clemente, E P ; Enríquez, J A ; Bernad, A ; Samper, E

England: Nature Publishing Group

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