Description
Cardiac Progenitor Cells (CPCs) are clonogenic and proliferative in vitro, and can differentiate into cardiomyocytes, smooth muscle cells and endothelial cells in-vivo. On the other hand, Mesenchymal Stem Cells (MSC), are known to augment proliferation, migration, recruitment and survival of CPCs by paracrine mediated effects. Combinatorial stem cell delivery strategy using CPCs and MSCs enhances myocardial repair and function in a large animal model of Myocardial Infarction (MI) compared to either cell population. Based on the preclinical studies, the currently ongoing phase 2 CONCERT HF-trial is comparing the safety and efficacy of bone marrow MSC, c- Kit+ CPCs and their combination in patients with ischemic cardiomyopathy. The goal of this study is to create Human CardioChimeras (HCCs) formed by fusion of human cardiac derived CPCs and MSCs and assess their phenotypic properties in-vitro compared to either parental cells. The hypothesis is that Human CardioChimeras (HCCs) demonstrate enhanced functional responses in-vitro relative to both the parental cells. The results show that cell fusion can generate phenotypically and morphologically distinct HCCs. In summary, HCCs derived by fusion demonstrated significant increases in proliferation and doubling time, and upregulated mRNA expression for cardio-myogenic and endothelial commitment markers relative to either parental cells. HCCs also demonstrated significant mRNA upregulation for Heparin Binding Epidermal Growth Factor and Fibroblast Growth Factor important for wound healing, cardiac development, proliferation and angiogenesis, under basal conditions. HCCs were also found to be significantly resistant to oxidative stress and ischemia-reperfusion injury and demonstrated significantly higher survival rates relative to both the parental cells. Over all, these results suggest that HCCs possess enhanced phenotypic properties and cellular stress resistance in-vitro compared to parental cells. HCCs emerge as superior hybrid cells to augment stem cell properties.
