Mesenchymal stem cells and hypoxia: Where are we?

• Hypoxic effects on MSC behavior are biphasic
• Oxygen concentration is critical as it largely contributes to MSC physiology
• Hypoxia-mediated mitochondrial silencing makes MSCs resistant to death inducers

Multipotent mesenchymal stromal cells (MSCs) are involved in the organization and maintenance of tissue integrity. MSCs have also attracted attention as a promising tool for cell therapy and regenerative medicine. However, their usage is limited due to cell impairment induced by an extremely harsh microenvironment during transplantation ex vivo. The microenvironment of MSCs in tissue depots is characterized by rather low oxygen consumption, demonstrating that MSCs might be quite resistant to oxygen limitation. However, accumulated data revealed that the response of MSCs to hypoxic conditions is rather controversial, demonstrating both damaging and ameliorating effects. Here, we make an attempt to summarize recent knowledge on the survival of MSCs under low oxygen conditions of varying duration and severity and to elucidate the mechanisms of MSC resistance/sensitivity to hypoxic impact.