Clinical Cardiology Stem Cell Applications

Until recently, traditional thinking held that no new cardiomyocytes are produced in postnatal life. Because human myocardial infarction heals mostly by collagenous scar formation rather than regeneration of contractile myocardium, there seemed little reason to question this paradigm during the twentieth century. However, the early years of this century have brought definitive demonstrations of dividing cardiomyocytes (or precardiomyocytes) after myocardial damage in animals1 and humans.2 In addition, based on 14C labeling of human DNA, the concept of postnatal endogenous regeneration of the adult heart is now firmly established.3 Rather than being born with all the cardiomyocytes that will ever exist, the normal adult human heart actually has a small rate of homeostatic cellular turnover, with about 1-2% of cardiomyocytes replaced per annum.3 Furthermore, populations of endogenous resident cardiac stem cells have been described, 4-9 and in some cases these cells have been shown to have clonal capacity and demonstrated an ability to differentiate into smooth muscle cells, endothelial cells, or cardiomyocytes.4, 8-10 These recent insights into basic cardiac biology have allowed for the rational consideration of the concept of myocardial regeneration and potential clinical applications. Some suggested cardiac clinical applications of stem cell therapy include regeneration of contractile myocardium, cellular revascularization for cases of ischemic cardiomyopathy in which percutaneous or surgical revascularization are not possible, and cellular therapy for bradyarrhythmias-a so-called biological pacemaker.11.