C-kit-positive cardiac stem cells and myocardial regeneration.

Two distinct subpopulations of endogenous cardiac stem cells (CSCs) are identified in the adult heart; myogenic CSCs (mCSCs), which are characterized by the presence of c-kit receptor, reside in the myocyte niche surrounded by matured cardiomyocytes, whereas vasculogenic CSCs (vCSCs), which express c-kit as well as KDR, are stored in the vascular niche found in the vessel wall. They both possess the fundamental properties of stem cells: self -renewing, clonogenic, and multipotent. While mCSCs preferentially differentiate into myocyte lineage in vitro, vCSCs tend to commit to vascular endothelial or smooth muscle lineages upon stimulation. Intramyocardial injection of human mCSCs to the region bordering infarct of immunosuppressed animals induces cardiac regeneration involving intensive muscle and vessel formation. On the other hand, the administration of human vCSCs near the critical stenosis created in the dog coronary artery results in the formation of large conductive vessels, i.e. "biological coronary bypass", coupled with the improved tissue perfusion. A clinical trial utilizing autologous c-kit-positive CSCs on patients with chronic ischemic heart failure was launched recently. Upon coronary artery bypass graft (CABG) surgery, a small portion of the right atrial appendage was obtained and used for isolation and expansion of CSCs. Intracoronary CSC implantation was performed 4 months after the surgery, and the symptom and the cardiac function were followed. Although the study is still ongoing, no adverse event due to cell infusion has been reported in any of the cell-treated patients, and the initial outcome is very promising. Disease-based customized cell therapy employing various combinations of autologous mCSCs and vCSCs would become available in the near future.