Stem Cells Review Series

Abstract

Cell therapy holds great promise for the treatment of cardiovascular disease. For the past 2 decades, investigators have been developing methods to implant various types of cells to heal the heart and improve the recovery of the heart after ischemia. Although multiple experimental and several clinical studies showed that different subsets of bone marrow–derived cells and other adult progenitor cells improved the recovery of heart function, the mechanism of action and the extent to which adult progenitor cells are able to restore cardiac function in end-stage heart failure is debated extensively. Therefore, this review series will summarize the current status of cell therapy in clinical trials and discuss the potential of different cell types and ways to enhance their functions. Additionally, epigenetic molecular mechanisms that regulate stem cell functions and fate decisions will be summarized. The first evidence that cell therapy may constitute a therapeutic option for the treatment of ischemic disease was provided by Asahara et al in 1997, who showed that bone marrow–derived CD34+ cells can give rise to endothelial-like cells and improve neovascularization after ischemia.1 In attempts to replace cardiomyocytes, initial animal studies used isolated neonatal cardiomyocytes to replace dead muscle tissue. Because of the limited availability of mature human cardiomyocytes, skeletal muscle cells were considered as an alternative cell source, which indeed improved cardiac function after transplantation of the cells in animal models. Subsequent clinical trials showed some benefit but also raised safety concerns with respect to arrhythmic events induced by nonintegrated skeletal muscle cells.2 Cultured cardiac stem cells, …