At a Crossroad

Abstract

Heart failure is a highly prevalent, debilitating, and costly condition with generally poor clinical outcomes.1 Aside from heart transplantation, which is an available treatment option for only a small fraction of patients because of donor organ shortage,2 there is no effective therapy that can reverse the course of this disease. A single episode of myocardial infarction may result in the loss of 1 billion cardiomyocytes or more (≈25% of total cardiomyocytes).3 Given the limited intrinsic capacity of the adult heart to repair itself, the goal of cardiac regenerative medicine has centered on strategies to remuscularize the diseased heart. Conceptually, the functional regeneration of an infarcted heart would entail the replacement of lost myocardium by aligned, electrically coupled, and mature new cardiomyocytes that beat in synchrony with the host myocardium. Beyond achieving this remarkable result, the avoidance of procedure-related complications and other potential adverse events, such as tumor formation or cardiac arrhythmia, is paramount for the therapy to be considered a success. While the process of finding the most appropriate cell type and delivery approach to achieve this objective has been the holy grail of cardiac regenerative medicine, a growing body of literature has now documented our initial efforts in this area. From these studies, the encouraging finding is that cell transplantation into the diseased heart (via intracoronary, transendocardial, or direct epicardial injection) appears to be reasonably safe. Furthermore, the practicalities of harvesting, expanding, and reintroducing cells back into the patient do not seem too cumbersome. However, the sobering reality we have learned is that tremendous roadblocks exist in achieving significant improvement in long-term cardiac function and bona fide remuscularization after cell transplantation. We believe the field of cardiac regeneration is at a crossroad. Although ongoing debate regarding the most appropriate cell type, timing, route of delivery, and …