title: Low oxygen tension enhances proliferation and maintains stemness of adipose tissue-derived stromal cells.
abstract: Recent evidence indicates that low oxygen tension or hypoxia alters the characteristics of stem cells. The actions of hypoxia are mediated through the hypoxia-inducible factor, a critical mediator of the cellular response to hypoxia. Adipose tissue-derived stromal cells (ASCs) are one of the most promising cell sources for tissue engineering applications. This study investigated the effect of hypoxia on ASCs in terms of the ability to proliferate and differentiate. ASCs were extracted from mice and maintained under hypoxic atmosphere (2% O2) for up to eight in vitro passages. The proliferation rate was examined as a growth curve, and the potency of differentiation was evaluated. To investigate the cell characteristics, we checked several stem-cell markers and growth factors. Compared with the normoxic state (20% O2), hypoxia enhances proliferation with an approximately six- to sevenfold higher ASC expansion over 6 weeks. The expression of Oct3/4 and Nanog (stem-cell marker) and the amount of secreted growth factors were increased under the hypoxic condition. These results suggest that low oxygen tension enhances proliferation and maintains stemness of ASCs. Thus, this study emphasizes the profitability of hypoxic culture for expansion of ASCs and maintenance of their undifferentiated state for further therapeutic use.
authors.affiliation: Division of Environmental Medicine, National Defense Medical College Research Institute , National Defense Medical College, Tokorozawa, Japan .
authors.forename: Yoritsuna
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Fujita
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kanatani
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishihara
authors.forename: Shoichi
authors.initials: S
authors.lastname: Tachibana
keywords: cell growth; differentiation; hypoxia; hypoxia-inducible factor; stem cell