The role of hypoxia in stem cell differentiation and therapeutics

Abstract

Stem cells differentiate into a variety of cell lines, making them attractive for tissue engineering and regenerative medicine. Specific microenvironmental cues regulate self-renewal and differentiation capabilities. Oxygen is an important component of the cellular microenvironment, serving as both metabolic substrate and signaling molecule. Oxygen has been shown to have a variety of effects on embryonic and adult stem cells. This review examines the role of hypoxia in regulating stem cell biology, specifically focusing on growth, maintenance of pluripotency, differentiation, and production of growth factors. Particular attention is paid to hypoxia and stem cells in relation to therapeutic angiogenesis. We conclude that further study is needed to optimize the use of hypoxia as a stimulus for various stem cell functions, including its potential role in therapeutic angiogenesis.

Figure

Algorithm of treatment for patient presenting with coronary artery or peripheral vascular disease. If the patient is not a candidate for standard revascularization options, cell-based therapeutic angiogenesis may be an option. Areas of future research should define which tissue source is most optimal for promoting angiogenesis, the ideal pre-conditioning strategy using hypoxia prior to use, as well as the most efficacious route of administration. Hypoxia may prove to be a useful stimulus for both culture expansion and stimulating cytokine expression.