Characterization of rat very small embryonic-like stem cells and cardiac repair after cell transplantation for myocardial infarction

Abstract

Stem cell therapy is a promising therapeutic strategy for treating myocardial infarction (MI). However, it is necessary to identify ideal adult stem cells for transplantation and explore mechanisms of the transplanted cells in improving cardiac functions after MI. In this study, a population of embryonic-like stem cells (ELSCs) was isolated from rat bone marrow. The cells express pluripotent stem cell transcriptional factors and present high proliferative activity on mouse embryonic fibroblast feeder. ELSCs retain clonal expansion and may form embryoid-like bodies in soft agarose containing leukemia inhibitory factor and basic fibroblast growth factor. The cells of the embryoid-like bodies can differentiate into the cells from 3 germ layers. Under induction, the cells can differentiate into cardiomyocytes and endothelial cells. In MI models of female rats, the transplantation of preinduced ELSCs of male rats reduce scar area and improve cardiac function significantly. Comparing with marrow-derived mesenchymal stem cells and ELSCs without induction, effects of the preinduced ELSCs on myocardial repair and improvement of cardiac function are greater. Survival of the transplanted cells in the peri-infarcted and infarcted regions was examined by fluorescence in situ hybridization. Y chromosome-positive cells may differentiate toward cardiomyocytes and express cTnT and Cx43. Cx43 expression was observed at conjunction of Y chromosome-positive cells and recipient cardiomyocytes. Some Y chromosome-positive cells express CD31 and incorporate into the microvessels in the infarcted tissue. These results suggest that a population of ELSCs resides in rat bone marrow and display similar biological characteristics of ESCs. ELSCs can differentiate into cardiomyocytes and endothelial cells and contribute to cardiomyogenesis and angiogenesis in vivo. Cardiac function after MI may be significantly improved with transplantation of the preinduced ELSCs. Therefore, ELSCs are novel seed cells for stem cell transplantation in regenerative medicine.