Triggering endogenous cardiac repair and regeneration via extracellular vesicle-mediated communication

A variety of paracrine signals create networks within the myocardium and mediate intercellular communications. Indeed, paracrine stimulation of the endogenous regenerative program of the heart, mainly based on resident cardiac progenitor cell (CPC) activation together with cardiomyocyte proliferation, has become increasingly relevant for future cardiac medicine. In the last years, it has been shown that extracellular vesicles (EV), including exosomes (Ex), are powerful conveyors of relevant biological effects. EV have been proposed not only as promising therapeutic tool for triggering cardiac regeneration and improving repair, but also as means of better understanding the physiological and pathological relationships between specific cardiac components, including cardiomyocytes and fibroblasts. Actually, EV from different kinds of exogenous stem cells have been shown to mediate beneficial effects on the injured myocardium. Moreover, endogenous cells, like CPC can instruct cardiovascular cell types, including cardiomyocytes, while cardiac stromal cells, especially fibroblasts, secrete EV that modulate relevant aspects of cardiomyocyte biology, such as hypertrophy and electrophysiological properties. Finally, cardiomyocytes too may release EV influencing the function of other cardiac cell types. Therefore, EV-based crosstalk is thought to be important in both physiology and pathology, being involved in the responses of the heart to noxious stimuli. Researchers from the University of Genova discuss the role of EV in both regulating cardiac homeostasis and driving heart regeneration. In particular, they address their role in: (i) providing cardio-protection and enhancing cardiac repair mechanisms; (ii) CPC biology; and (iii) influencing adult cardiomyocyte behavior.

Schematic representation of the most relevant effects of extracellular vesicle-mediated intercellular communication within the injured myocardium

exosomes

(A) cardio-protection and cardiac repair by exogenous stem cell-EV/Ex; (B) paracrine modulation of the cardiac microenvironment by EV/Ex derived from CPC either activated in situ (i) or previously isolated and expanded in vitro (ii); and (C) fine tuning of adult resident cardiomyocyte and cardiac stromal cell behavior by their mutual EV/Ex modulatory exchange during adaptive response to stress. ATMP, advanced therapy medicinal product.

Bollini S, Smits AM, Balbi C, Lazzarini E, Ameri P. (2018) Triggering Endogenous Cardiac Repair and Regeneration via Extracellular Vesicle-Mediated Communication. Front Physiol 9:1497. [article]

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