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Universal Cardiac Mesoangioblasts for treating DMD Dilated Cardiomyopathy

Project description

Regenerative treatment for cardiac diseases

Dilated cardiomyopathy (DCM) is a progressive heart muscle disorder associated with enlargement and impaired contraction of ventricles. DCM increases the risk of heart failure and death. The heart has a limited capacity for self-repair, and the existence of bona fide cardiac stem cells is still up for debate. Current stem cell therapies for DCM have shown minimal success due to immune rejection and insufficient cardiomyocyte differentiation. The ERC-funded UniCardioMab project builds on previous work in muscular dystrophy to create immortal, cardiac progenitor cells capable of evading immune responses. These cells will be primed with cardiac transcription factors to become cardiac stem cells and delivered to inflamed heart tissue, providing a novel regenerative strategy for treating otherwise irreversible cardiac damage.

Objective

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.

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2024-POC

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Host institution

OSPEDALE SAN RAFFAELE SRL
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 115 000,00
Address
VIA OLGETTINA 60
20132 Milano
Italy

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Region
Nord-Ovest Lombardia Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

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Beneficiaries (2)

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