Abstract
Adult stem cell-based therapeutic approaches for tissue regeneration have been proposed for several years. However, adult stem cells are usually limited in number and difficult to be expanded in vitro, and they usually tend to quickly lose their potency with passages, as they differentiate and become senescent. Culturing stem cells under reduced oxygen tensions (below 21%) has been proposed as a tool to increase cell proliferation, but many studies reported opposite effects. In particular, cell response to hypoxia seems to be very stem cell type specific. Nonetheless, it is clear that a major role in this process is played by the hypoxia inducible factor (HIF), the master regulator of cell response to oxygen deprivation, which affects cell metabolism and differentiation. Herein, we report that a chemical activation of HIF in human tendon stem cells reduces their proliferation and inhibits their differentiation in a reversible and dose-dependent manner. These results support the notion that hypoxia, by activating HIF, plays a crucial role in preserving stem cells in an undifferentiated state in the “hypoxic niches” present in the tissue in which they reside before migrating in more oxygenated areas to heal a damaged tissue.
Highlights
Stem cell-based therapies have promised to be an attractive approach in tissue regeneration, especially with the discovery that adult tissues possess a reservoir of progenitor cells that can be isolated and cultured in vitro [1]
To chemically activate hypoxia inducible factor (HIF)-1α, Human tendon stem cells (hTSCs) were cultured under normoxia in the presence of DMOG at different concentrations (0.01 mM, 0.1 mM, and 1 mM) for 96 h and compared to control cells that were cultured in normal growth medium without DMOG (Figure 2)
We found that stem cell markers Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT4), and Kruppel-like factor 4 (KLF4) are slightly upregulated upon DMOG supplementation and this increase is proportional to the DMOG concentration used
Summary
Stem cell-based therapies have promised to be an attractive approach in tissue regeneration, especially with the discovery that adult tissues possess a reservoir of progenitor cells that can be isolated and cultured in vitro [1]. One of the main obstacles that have been encountered is the relatively small number of adult stem cells present in tissues and their very limited proliferative capacity. A possible approach to overcome these limitations is to culture cells under low oxygen levels (below 21%) [2,3,4,5]. Maintaining the correct in vitro culturing conditions under reduced oxygen tensions is quite complex. We can speculate that these inconsistencies in the literature are likely due to a distinct response of each stem cell subtype to hypoxia.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
