Cell Therapy: Targeting Endogenous Repair Versus Remuscularization.

Abstract

A growing body of work supports cell-based therapeutics as a promising strategy for treating cardiovascular disease.1 Patients who receive stem cells, previously isolated from the bone marrow (eg, mesenchymal stem cells [MSCs])2–5 or the heart (cardiac stem cells [CSCs]),6,7 experience improved cardiac anatomy, increased functional capacity, and quality of life. With regard to MSCs and CSCs, scar tissue is reduced and replaced by contractile myocardium,2,3,6,7 accompanied by increased tissue perfusion, due most likely to neovascularization and improved endothelial function, globally8 and locally.1–5 Article, see p 695 Previous studies hypothesized that the therapeutic capacity of transplanted cells is derived from their ability to differentiate into cardiomyocytes.9 However, this concept has not yet been meaningfully achieved. In a recent study by Chong et al,9 nonhuman primates were administered 109 human embryonic stem cells–derived cardiomyocytes after myocardial infarction. In this study, they achieved engraftment but no functional recovery.9 Similar findings were recently reported by others.10 Thus, engraftment and differentiation are not sufficient for cardiac repair. In contrast, transplantation of cells with lower capacity to form new myocytes does significantly enhance repair.1 This seemingly paradoxical effect coupled …