title: Physiologically normal 5% O2 supports neuronal differentiation and resistance to inflammatory injury in neural stem cell cultures.
abstract: Recent studies have demonstrated that neural stem cell (NSC) culture at physiologically normoxic conditions (2-5% O2) is advantageous in terms of neuronal differentiation and survival. Neuronal differentiation is accompanied by a remarkable shift to mitochondrial oxidative metabolism compared with preferentially glycolytic metabolism of proliferating cells. However, metabolic changes induced by growth in a normoxic (5%) O2 culture environment in NSCs have been minimally explored. This study demonstrates that culturing under 5% O2 conditions results in higher levels of mitochondrial oxidative metabolism, decreased glycolysis, and reduced levels of reactive oxygen species in NSC cultures. Inflammation is one of the major environmental factors limiting postinjury NSC neuronal differentiation and survival. Our results show that NSCs differentiated under 5% O2 conditions possess better resistance to in vitro inflammatory injury compared with those exposed to 20% O2. The present work demonstrates that lower, more physiologically normal O2 levels support metabolic changes induced during NSC neuronal differentiation and provide increased resistance to inflammatory injury, thus highlighting O2 tension as an important determinant of cell fate and survival in various stem cell therapies.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Ludmila A
authors.initials: LA
authors.lastname: Voloboueva
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Creed M
authors.initials: CM
authors.lastname: Stary
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California.
authors.forename: Rona G
authors.initials: RG
authors.lastname: Giffard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006019:Glycolysis / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*
chemical_list: D010100:Oxygen
keywords: metabolism; mitochondria; neurogenesis; oxygen; stem cell