Paracrine Effects of Cell Transplantation: Strategies to Augment the Efficacy of Cell Therapies

Within the last few years, it has become evident that the beneficial effect of cell transplantation on ventricular function and myocardial perfusion is in large part mediated through paracrine effects on the host myocardium. Studies in which medium conditioned by cultured cells, usually mesenchymal stem cells, were injected into infarcted animal hearts have provided definitive evidence of this mechanism of action. Paracrine effects of the donor cells include but are not limited to angiogenesis, mobilization of both circulating and bone-marrow-derived stem cells, activation of cardiac-resident stem cells (CRSCs), and stabilization of the extracellular matrix (ECM). These paracrine effects can be augmented by transplantation of cells modified to express therapeutically useful transgenes, or by preconditioning through hypoxic or pharmacologic means. Strategies to enhance the paracrine effects of cell transplantation may thus be employed in the next generation of cell therapies, with greater functional benefit.