Chemical Activation of the Hypoxia-Inducible Factor Reversibly Reduces Tendon Stem Cell Proliferation, Inhibits Their Differentiation, and Maintains Cell Undifferentiation

摘要: Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed several years. However, adult cells are usually limited in number and difficult to be expanded vitro, they tend quickly lose their potency with passages, as differentiate become senescent. Culturing under reduced oxygen tensions (below 21%) has a tool increase cell proliferation, but many studies reported opposite effects. In particular, response hypoxia seems very type specific. Nonetheless, it is clear that major role this process played by the inducible factor (HIF), master regulator of deprivation, which affects metabolism differentiation. Herein, we report chemical activation HIF human tendon reduces proliferation inhibits differentiation reversible dose-dependent manner. These results support notion hypoxia, activating HIF, plays crucial preserving an undifferentiated state “hypoxic niches” present reside before migrating more oxygenated areas heal damaged tissue.