Regulation of Hypoxia-Induced Cell Death and Application of Hypoxic Preconditioning to Stem Cell Transplantation

Hypoxia is a commonly encountered feature of the cellular microenvironment in a number of processes in which programmed cell death (apoptosis) affects disease progression. These diseases include myocardial infarction, stroke, and ischemic acute kidney injury. Bone marrow-derived mesenchymal stem cells (MSCs) are multipotent adult stem cells that are able to differentiate into endothelial cells, vascular smooth muscle cells, or cardiac-like myocytes when transplanted into the ischemic heart. Both animal and clinical studies have substantiated that MSC transplantation can enhance cardiac function through possible angiogenesis and myogenesis after myocardial infarction. However, some studies have failed to monitor the therapeutic effects of MSC transplantation; therefore, there is a need for supplementary research on the use of MSCs and the improvement of transplantation techniques after MI. An important problem in stem cell therapy for ischemic heart diseases is the low survival of transplanted cells in the ischemic and infarcted sites. Most transplanted cells die within 4 days after transplantation into the ischemic heart. Endogenous and environmental factors, such as hypoxia and inflammatory response, may contribute to cell death. Therefore, enhancing implanted cell survival after transplantation is vital for improving the effect and efficiency of stem cell therapy. In this review, we investigate whether hypoxia is responsible for activating apoptosis signaling in transplanted stem cells, and could be a potential target for enhancing the therapeutic effect of stem cells in treating ischemic heart diseases.