Our objective is still to develop a cell therapy product targeted at the repair of the chronically failing myocardium and based on the use of cardiac progenitor cells derived from induced pluripotent stem cells. However, recognizing that the primary mechanism of action of the cells is a paracrine harnessing of endogenous repair pathways, we have now moved away from the transplantation of the cells themselves and try to leverage these paracrine effects by the exclusive delivery of their extracellular vesicle-enriched secretome. At the same time, we work on two approaches for delivering this biological medication: the incorporation of the cellular secretome in a controlled-release hydrogel delivered onto the epicardium of the heart if a surgical procedure is required and, at the opposite of this invasive route, an intravenous infusion if no surgery is indicated. In the latter case, we explore the possibility of enhancing the cardiac homing of this systemically delivered secretome by engineering the glycan surface repertoire of its extracellular vesicles in a way that could foster their interactions with myocardium-specific receptors. A clinical trial is planned (and funded) and its translational steps are under way.
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Partner Team