Universal Cardiac Mesoangioblasts for treating DMD Dilated Cardiomyopathy

Introduction

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 DCM with stem cells, their extracellular vesicles, or AAV vectors; however, none have reached efficacy so far.

Background

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 DCM, but a simple extension of this strategy is problematic since the existence of resident cardiac stem cells is controversial. Additionally, cardiac mesoangioblasts do not spontaneously differentiate into cardiomyocytes.

Current Research

iPS cell-derived cardiac progenitors are promising but have, until now, been used for localized lesions such as myocardial infarcts. To address this problem, we will produce immortal, immune-privileged cardiac mesoangioblasts and will convert them to cardioblasts through in vitro expression of cardiac transcription factors.

Methodology

Since conversion takes about two weeks, we will test different settings to allow cells to home and differentiate in vivo in the areas of damage, characterized by inflammation.

Future Directions

The applicant is in a unique position to test the feasibility of this project for future translation into a novel clinical protocol.