Paracrine Effects of Cell Transplantation: Modifying Ventricular Remodeling in the Failing Heart

Abstract

Structural ventricular remodeling determines the clinical progression of heart failure and has emerged as an important target for the development of novel medical and surgical therapeutic strategies. Cell transplantation is an innovative biologic therapy that may restore myocardial structure and function in failing hearts. With current forms of cell transplant therapy, true myocardial regeneration has been limited. However, cell transplantation can predictably limit maladaptive ventricular remodeling through multiple synergistic paracrine mechanisms. Some of the paracrine factors released by transplanted cells have been defined. These paracrine signals may provide beneficial effects by stimulating angiogenesis, limiting matrix disruption, and preventing apoptosis. In addition, cell transplantation may induce mobilization and homing of endogenous repair cells to injured myocardium through paracrine signals. Paracrine mediators released from transplanted cells work through multiple, diverse, and interrelated molecular pathways resulting in synergistic effects on the remodeling process. Although true myocardial regeneration remains the ultimate goal of cell therapy, the anti-remodeling abilities of cell transplantation can be harnessed to complement our contemporary surgical approaches for patients with myocardial injury at risk of congestive heart failure.