Review Article: Current Status of Myocardial Regeneration: New Cell Sources and New Strategies

Abstract

Clinical trials of stem cell therapy in cardiology are based upon a reasonably solid foundation in animal laboratory research. The most widely used cell source in clinical trials has been the patient’s own reconstituted bone marrow cell (BMC) aspirate. Cell sources in human bone marrow include hematopoietic stem cells, mesenchymal progenitor cells, and other cell types with many desirable characteristics. In vitro, they can be induced to become typical sarcomeres with centrally positioned nuclei and abundant mitochondria and to express atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and contractile proteins including myosin heavy chain, myosin light chain, and alpha actin. Intracoronary BMC infusion significantly decreases infarct size, increases myocardial perfusion, and improves regional and global cardiac function. Meta-analyses of clinical trials of intracoronary autologous BMC infusion following acute myocardial infarction (MI) report that the mean absolute increase in ejection fraction (EF) is approximately 3% to 4%. This modest improvement in function appears to persist for 1 year. Some trials have shown that clinical events are reduced at 12 months, but others have reported no long-term clinical benefit, and the only 5-year follow-up suggests persistent benefit with decreased mortality, but also little evidence of significant myocardial regeneration in humans. These results have led to efforts to identify better cell sources and to create more conducive myocardial environment for cell proliferation. Among the cell types are skeletal myoblasts, cardiac stem cells, and induced pluripotent stem cells. Environmental modifiers are designed to increase cell survival, persistence, and proliferation.