Insight into Hypoxia Stemness Control

Recently, the research on stemness and multilineage differentiation mechanisms has greatly increased its value due to the potential therapeutic impact of stem cell-based approaches. Stem cells modulate their self-renewing and differentiation capacities in response to endogenous and/or extrinsic factors that can control stem cell fate. One key factor controlling stem cell phenotype is oxygen (O-2). Several pieces of evidence demonstrated that the complexity of reproducing O-2 physiological tensions and gradients in culture is responsible for defective stem cell behavior in vitro and after transplantation. This evidence is still worsened by considering that stem cells are conventionally incubated under non-physiological air O-2 tension (21%). Therefore, the study of mechanisms and signaling activated at lower O-2 tension, such as those existing under native microenvironments (referred to as hypoxia), represent an effective strategy to define if O-2 is essential in preserving naive stemness potential as well as in modulating their differentiation. Starting from this premise, the goal of the present review is to report the status of the art about the link existing between hypoxia and stemness providing insight into the factors/molecules involved, to design targeted strategies that, recapitulating naive O-2 signals, enable towards the therapeutic use of stem cell for tissue engineering and regenerative medicine.

Automated summary

This research highlights the impact of oxygen on stem cell stemness and multilineage differentiation, emphasizing the signaling mechanisms activated under low oxygen tension and how targeted strategies can be designed to enhance the therapeutic applications of stem cells in tissue engineering and regenerative medicine.