Exosomes delivered by human cardiac primitive cells impact on both cardiac cellular and extracellular compartment

Although human Cardiac Primitive Cells (CPC) when injected in infarcted heart are not retained by host myocardium, they improve cardiac function. Emerging evidence supports the hypothesis that exosomes may be responsible for beneficial effects induced by stem cells delivered in the infarcted myocardium. Exosomes are nano-sized vesicles naturally secreted by almost all cells and ubiquitously found in cell culture supernatants and biological fluids. Transporting and transferring peptides, lipids, and nucleic acids, exosomes have the potential to modulate signaling pathways, cell growth, migration, and proliferation of recipient cells. Accordingly, CPC may deliver chemoattractive, pro-survival and differentiating signals to resident cells through exosomes. To test our hypothesis, we isolated exosomes released in culture by CPC isolated from adult human myocardium (Exo-CPC) and analyzed the composition of their cargo. Specifically, we searched for the presence of specific factors known to regulate CPC migration, survival and differentiation, as HGF, IGF, TGF, Nkx2.5, Tbx, and Mef2c. Additionally, we tested in vitro the potential of Exo-CPC of either regulating CPC proliferation and programmed cell death, and modulating interstitial fibrosis, extracellular-matrix (ECM) synthesis and deposition. Interestingly, on one hand, signals delivered by Exo-CPC affected proliferation and survival of CPC and, on the other hand, regulated ECM proteins production. Therefore, we might speculate that Exo-CPC have potential effect on both resident CPC and fibroblasts when injected in cardiac wall.