title: Culture of human mesenchymal stem cells at low oxygen tension improves growth and genetic stability by activating glycolysis.
abstract: 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.
authors.affiliation: Department of Regenerative Cardiology, Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III, Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
authors.forename: J C
authors.initials: JC
authors.lastname: Estrada
authors.forename: C
authors.initials: C
authors.lastname: Albo
authors.forename: A
authors.initials: A
authors.lastname: Benguría
authors.forename: A
authors.initials: A
authors.lastname: Dopazo
authors.forename: P
authors.initials: P
authors.lastname: López-Romero
authors.forename: L
authors.initials: L
authors.lastname: Carrera-Quintanar
authors.forename: E
authors.initials: E
authors.lastname: Roche
authors.forename: E P
authors.initials: EP
authors.lastname: Clemente
authors.forename: J A
authors.initials: JA
authors.lastname: Enríquez
authors.forename: A
authors.initials: A
authors.lastname: Bernad
authors.forename: E
authors.initials: E
authors.lastname: Samper
mesh_terms: D000782:Aneuploidy; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D043171:Chromosomal Instability / Q000235:genetics; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000235:genetics; D010100:Oxygen / Q000378:metabolism*; D016615:Telomere / Q000235:genetics
chemical_list: D010100:Oxygen