Universal Cardiac Mesoangioblasts for treating DMD Dilated Cardiomyopathy

ongoing

Dilated cardiomyopathy (DCM) is the second most common cause of heart failure, currently treated with drugs that delay progress towards heart transplantation. There are currently many attempts to treat DC with stem cells or their extracellular vesicles or AAV vectors: none reached efficacy so far. The applicant has a long track record in cell and gene therapy for muscular dystrophy. He pioneered systemic intra-arterial transplantation of mesoangioblasts (blood vessel-derived progenitors) and, thanks to a previous ERC grant, succeeded in creating immortal, universal donor mesoangioblasts. Edited cells do not activate an immune response in vitro or in vivo. Muscular dystrophy also affects the heart causing a DCM, but a simple extension of this strategy is problematic since the existence of resident cardiac stem cells is controversial and cardiac mesoangioblasts do not spontaneously differ-entiate into cardiomyocytes. iPS cell-derived cardiac progenitors are promising but until now for lo-calised lesions such as myocardial infarcts. To address this problem we will produce immortal, im-mune privileged cardiac mesoangioblasts and will convert them to cardioblasts, in vitro expression of cardiac transcription factors. Since conversion takes about two weeks, we will test different settings to allow cells so that they would home and differentiate in vivo in the areas of damage, characterized by inflammation. The applicant is in the unique position to test feasibility of this project for future translation into a novel clinical protocol.