Meta-Analysis of Preclinical Data Reveals Efficacy of Cardiac Stem Cell Therapy for Heart Repair.

Abstract

Cell therapy has rapidly emerged as a potential option for cardiac repair in patients with ischemic heart disease. Since the turn of the century, several forms of cell therapy have been evaluated in clinical trials, including skeletal myoblasts, bone marrow mononuclear cells, mesenchymal stem cells, and cardiac stem cells (CSCs). Cell therapy, in its various forms, has generally been efficacious, providing modest improvements in cardiac structure and function in patients with acute myocardial infarction (MI), as well as chronic ischemic heart disease.1 Although bone marrow cells are relatively easy to harvest and deliver, these are not natural residents of cardiac tissue, and their ability to regenerate lost myocardium remains controversial. In the absence of an obvious choice, the search for newer cellular substrates has continued. Article, see p 1223 In 2003, Beltrami et al2 described the existence of c-kit+ cells in the heart, which were reported to be self-replicating, clonogenic, and multipotent, giving rise to cardiomyocytes, smooth muscle cells, and new blood vessels in ischemic rat hearts. Subsequent demonstration of heart repair with intravascular delivery of c-kit+ CSCs paved the way for clinical translation using intracoronary delivery.3 Intense research in this area quickly resulted in the discovery of several additional types of cardiac progenitors, including cardiosphere-derived cells (CDCs), Sca-1+ cells, cardiac side population cells, Isl1+ cells, and epicardial progenitors, among others. Of these, c-kit+ CSCs and CDCs have already been tested in randomized controlled trials in humans. Intracoronary injection of culture-expanded autologous c-kit+ CSCs into hearts of ischemic cardiomyopathy patients improved left ventricular ejection fraction (LVEF) and reduced infarct size in the Stem Cell Infusion in Patients With Ischemic cardiomyopathy (SCIPIO) trial.4 Injection of autologous CDCs into the infarct-related artery reduced scar mass and increased regional contractility with a nonsignificant …