Promotion of Cardiac Regeneration by Cardiac Stem Cells

Abstract

See related article, pages 663–673 Research on myocardial regeneration is an exciting and promising area, which challenges the dogma that the heart is a nonregenerating organ. Recently, several methods of stem cell therapy have been developed. One method is to transplant cells into the infarcted area of the myocardium. Currently, clinical trials of autologous skeletal myoblast transplantation into the failed heart are underway and have been reported to improve the cardiac function.1 However, the mechanism of its efficacy is unknown, and there are some questions about the safety because myoblasts do not transdifferentiate into cardiomyocytes and may induce lethal arrhythmia.1 In this point, embryonic stem (ES) cells that can differentiate into cardiomyocytes are thought to be more promising.2 For patients experiencing extensive myocardial infarction or dilated cardiomyopathy, however, the effectiveness of cell transplantation is questionable. Bone marrow-derived cells have been reported to transdifferentiate into various types of cells in situ. Indeed, bone marrow-derived stem cells were reported to prevent left ventricular remodeling after myocardial infarction and improve cardiac function by their differentiation into cardiomyocytes.3 However, recent accumulating evidence has indicated that very few bone marrow cells, if any, transdifferentiate into cardiomyocytes.4–6 Cytokine therapy using G-CSF strongly prevents ventricular remodeling after myocardial infarction by antiapoptotic and angiogenic effects, but not by recruitment of bone marrow cells.7 Over the past few years, adult hearts have been reported to contain the cardiac stem/progenitor cells such as c-kit+,8 Sca-1+,9,10 isl-1+,11 and side population cells.12 Because these cells have the ability to proliferate and …