Enhanced Proliferation and Cardiogenic Differentiation of Cardiac Progenitor Cells Treated with a Naturally Derived Cardiac Extracellular Matrix

Adverse remodeling of the myocardium after myocardial infarction speeds progression to heart failure. Some of the major shortcomings in cell therapy are the growth and differentiation of implanted cells. In patients, cells are injected to an area comprised mostly of noncontractile collagen, far different from their native microenvironment. This study aims to determine whether a naturally derived porcine cardiac extracellular matrix (cECM) enhances proliferation and differentiation in cardiac progenitor cells (CPCs). CPCs were isolated via magnetic sorting of c‐kit + cells in cardiac tissue homogenates and were grown on plates coated with either cECM or collagen I (COL). Greater serum‐induced proliferation was seen on cECM as compared to COL (3.17 vs. 1.99‐fold) as measured by Coulter counting at 2 days. Further, a trend toward increased expression of cardiac markers (Nkx2.5 and GATA4) was seen at this early time point. At 7 days, protein levels of Nkx2.5 and GATA4 were increased. Finally, fibroblastic markers were decreased at 7 days, while the environment of the cells had become oxidative, compatible with reports of redox regulation during differentiation. Our data demonstrate that a naturally derived matrix may provide enhanced proliferation and cardiogenic differentiation of CPCs compared to collagen and thus may be a suitable vehicle to deliver cells in vivo . This study was supported by internal funding.