Personalized therapy for human heart diseases with the exosomes generated from iPSC derived cardiomyocytes

Cardiovascular disease (CVD) is the leading cause of death in modern society. The adult heart innately lacks the capacity to repair and regenerate the damaged myocardium from ischemic injury. Limited understanding of cardiac tissue repair process hampers the development of effective therapeutic solutions to treat CVD such as ischemic cardiomyopathy. In recent years, rapid emergence of induced pluripotent stem cells (iPSC) and iPSC-derived cardiomyocytes presents a valuable opportunity to replenish the functional cells to the heart. The therapeutic effects of iPSC-derived cells have been investigated in many preclinical studies. However, the underlying mechanisms of iPSC-derived cell therapy are still unclear, and limited engraftment of iPSC-derived cardiomyocytes is well known. One facet of their mechanism is the paracrine effect of the transplanted cells. Microvesicles such as exosomes secreted from the iPSC-derived cardiomyocytes exert protective effects by transferring the endogenous molecules to salvage the injured neighboring cells by regulating apoptosis, inflammation, fibrosis, and angiogenesis.

Exosomes from patient-specific iPSC derivatives provide a platform for personalized therapy by simulating endogenous repair. Exosomes can be directed to specific injured site of each individual patient to promote salvage of the existing injured cardiac cells. Exosomes isolated from the supernatant of iCM culture undergo ultracentrifugation methods, as well as advanced characterization and quantification by transmission electronical microscopy, Nanosight, and dynamic light scattering.