Overcoming the Roadblocks to Cardiac Cell Therapy Using Tissue Engineering

Abstract

Transplantations of various stem cells or their progeny have repeatedly improved cardiac performance in animal models of myocardial injury; however, the benefits observed in clinical trials have been generally less consistent. Some of the recognized challenges are poor engraftment of implanted cells and, in the case of human cardiomyocytes, functional immaturity and lack of electrical integration, leading to limited contribution to the heart's contractile activity and increased arrhythmogenic risks. Advances in tissue and genetic engineering techniques are expected to improve the survival and integration of transplanted cells, and to support structural, functional, and bioenergetic recovery of the recipient hearts. Specifically, application of a prefabricated cardiac tissue patch to prevent dilation and to improve pumping efficiency of the infarcted heart offers a promising strategy for making stem cell therapy a clinical reality.

Keywords: biocompatible materials; heart failure; myocardial infarction; myocardium; stem cells.

Central Illustration. Overview of Strategies to Overcome the Roadblocks in Cardiac Cell Therapy

The delivery of types of cells generally resulted in modest therapeutic benefits. Transplantation of prefabricated engineered heart tissue (e.g., cardiac tissue patch containing pluripotent stem cell–derived tri-cardiac cells) could enhance the therapeutic effects by an increased engraftment rate, which in turn, results in prolonged release of cytokines, reduction in left ventricular (LV) dilation and LV wall stresses. A major challenge that remains to be addressed is the potential arrhythmia risks associated with a large graft.