Role of Stem Cell–Derived Microvesicles in Cardiovascular Disease

Abstract: The role of stem cells in augmenting reparative processes in the heart after ischemic injury has been successfully demonstrated in small and large animal models. However, the outcomes of cell therapy in clinical trials have been somewhat variable, with overall effects of autologous stem cell therapies demonstrating a modest improvement in cardiac structure and function. How stem cells repair the heart after cardiac injury is still not well understood. Most recent studies suggest that adult derived stem cells act primarily through paracrine signaling to exert beneficial effects, including modulation of immune response, stimulation of new blood vessel formation, or by inducing mature myocytes to transiently reenter the cell cycle, rather than robust direct differentiation of the transplanted cells into myocytes. In addition, data from multiple laboratory results confirmed clearance of stem cells themselves within a few days still leading to functional benefits further confirming the role of paracrine signaling in augmenting cardiac reparative processes rather than direct differentiation of cells. These findings rapidly evolved the field of extracellular vesicles specifically microvesicles (MVs) as they are active hubs of autocrine, paracrine, and endocrine signaling targeting different biological processes. The beneficial effects seen after stem cell transplantation could be linked to the cardioprotective factors packaged in the MVs secreted from stem cells. Therefore, stem cell MVs provide a new avenue for the treatment of cardiovascular disease through a multitude of mechanisms including cellular communication within the stem cell niches, delivery of genetic information, regulation of the immune system in the heart, and stimulation of angiogenesis which will be discussed in this review.