Exosomes as potential alternatives to stem cell therapy in mediating cardiac regeneration.

Abstract

Cardiovascular diseases represent a significant cause of death and disability worldwide.1 The decline of cardiovascular mortality as a result of modern medicine and surgery has in turn led to a rapid increase of patients having heart failure, with the only definite cure being heart transplantation. However, many patients are unable to undergo transplantation surgery because of complications from existing comorbidities, and among suitable patients, the procedure is plagued by limited donor supply, high costs, and the need for chronic immunosuppressant therapy. Hence, recent advances in cardiac regenerative therapy have emerged as an attractive alternative. Article, see p 52 Currently, there are several methods to achieve cardiac regeneration. Endogenous cardiac repair that involves generation of new cardiomyocytes from differentiation of cardiac progenitor cells (CPCs) or renewal of pre-existing adult cardiomyocytes is one such approach, albeit a rare and inefficient process to cope with the loss of cardiomyocytes after myocardial infarction or other cardiac diseases.2 Alternatively, functional myocardium may be salvaged or replenished through transplantation of exogenous stem cells.3,4 However, the poor long-term engraftment and survival in current transplantation have largely precluded substantial cell replacement, and instead supports the paracrine hypothesis that the release of external factors contributes to myocardial salvage or repair. Historically, the paracrine hypothesis is thought to be mediated primarily by chemical and physical signals, such as soluble proteins, gene products, lipids, and gases. Indeed, various studies have demonstrated that stem cells produce and secrete a broad range of cytokines, chemokines, and growth factors that are involved in cardiac repair.5 Strong support of a paracrine hypothesis came from experimental studies in which the administration of conditioned medium from stem cells was able to confer beneficial effects without the physical presence of stem cells within the infarcted heart.5,6 There is a …