How do resident stem cells repair the damaged myocardium?

Abstract

It has been a decade since the monumental discovery of resident stem cells in the mammalian heart, and the following studies witnessed the continuous turnover of cardiomyocytes and vascular cells, maintaining the homeostasis of the organ. Recently, the autologous administration of c-kit-positive cardiac stem cells in patients with ischemic heart failure has led to an incredible outcome; the left ventricular ejection fraction of the cell-treated group improved from 30% at the baseline to 38% after one year and to 42% after two years of cell injection. The potential underlying mechanisms, before and after cell infusion, are explored and discussed in this article. Some of them are related to the intrinsic property of the resident stem cells, such as direct differentiation, paracrine action, and immunomodulatory function, whereas others involve environmental factors, leading to cellular reverse remodeling and to the natural selection of “juvenile” cells. It has now been demonstrated that cardiac stem cells for therapeutic purposes can be prepared from tiny biopsied specimens of the failing heart as well as from frozen tissues, which may remarkably expand the repertoire of the strategy against various cardiovascular disorders, including non-ischemic cardiomyopathy and congenital heart diseases. Further translational investigations are needed to explore these possibilities.

Keywords: Regeneration; Heart failure; Cell therapy; C-kit; Cardiac stem cells; Cellular reverse remodeling; Mircrine

Core tip: The autologous transplantation of cardiac stem cells appeared to be safe and surprisingly effective for a small group of patients with chronic ischemic cardiomyopathy. Their specific feature as resident stem cells, the interaction with the surrounding tissue, and the natural selection during the cell culture process potentially contributed together to the outstanding consequences.