Electrophysiological Coupling of Transplanted Cardiomyocytes

Abstract

See related article, pages 484–492 The recent advances in stem cell biology and tissue engineering have paved the way to the development of a new field in biomedicine, regenerative medicine. This approach seeks to circumvent the shortage of organs for transplantation, by combining the above-mentioned technologies in an attempt to replace diseased or absent tissue. The heart represents an attractive candidate for these emerging technologies, and myocardial cell replacement therapy and tissue engineering present exciting new possibilities for assisting the failing myocardium.1,2 Despite the enormous enthusiasm associated with cardiovascular regenerative medicine, several obstacles need to be overcome before such strategies can become a clinical reality. Among the major targets that must be achieved are the needs to find an efficient cell source, which will provide the large number of cardiomyocytes required, overcoming the immune rejection barrier of nonautologous cell sources, and finding means for directing stem cells to differentiate to the cardiomyocyte lineage. Yet, concentration on these “major” unanswered questions may lead one to believe that all other issues with cell therapy have been solved. A closer inspection, however, reveals that this is not the case and many questions still remain open. Even if we could identify the ideal stem cell source, could direct the differentiation of these cells efficiently to cardiomyocytes, and prevent immune rejection we still do not know how many cells should be transplanted, what is the best timing and sites for cell transplantation, and most importantly whether the engrafted cells would survive and integrate appropriately with the existing cell-network of host cardiac tissue. Numerous reports suggest that myocyte transplantation can improve cardiac performance in animal models of myocardial infarction.1,2 However, it is not entirely clear whether this functional improvement is attributable to direct contribution to contractility by the transplanted myocytes or by other …