Discrepancies on the Role of Oxygen Gradient and Culture Condition on Mesenchymal Stem Cell Fate

Over the past few years, mesenchymal stem (or stromal) cells (MSCs) have garnered enormous interest due to their therapeutic value especially for their multilineage differentiation potential leading to regenerative medicine applications. MSCs undergo physiological changes upon in vitro expansion resulting in expression of different receptors, thereby inducing high variabilities in therapeutic efficacy. Therefore, understanding the biochemical cues that influence the native local signals on differentiation or proliferation of these cells is very important. There have been several reports that in vitro culture of MSCs in low oxygen gradient (or hypoxic conditions) upregulates the stemness markers and promotes cell proliferation in an undifferentiated state, as hypoxia mimics the conditions the progenitor cells experience within the tissue. However, different studies report different oxygen gradients and culture conditions causing ambiguity in their interpretation of the results. In this progress report, it is aimed to summarize recent studies in the field with specific focus on conflicting results reported during the application of hypoxic conditions for improving the proliferation or differentiation of MSCs. Further, it is tried to decipher the factors that can affect characteristics of MSC under hypoxia and suggest a few techniques that could be combined with hypoxic cell culture to better recapitulate the MSC tissue niche.

Automated summary

Studies have shown that culturing MSCs in a low oxygen environment can upregulate stem cell markers and promote cell proliferation in an undifferentiated state. However, there is ambiguity in the results due to differences in oxygen gradients and culture conditions among different studies. This progress report focuses on conflicting findings related to the application of hypoxic conditions for improving MSC proliferation or differentiation, aiming to decipher the factors influencing MSC characteristics under hypoxia.