Project description
New therapy for heart failure
During a heart attack, up to 25 % of cardiomyocytes in the left ventricle die, contributing to heart failure. Unlike other tissues, the adult heart cannot regenerate these lost cells. Supported by the Marie Skłodowska-Curie Actions programme, the CardioReGen project is developing a groundbreaking therapy using lipid nanoparticles to deliver pro-proliferative microRNAs. This method, proven effective in mice and pigs, avoids the safety concerns associated with viral gene delivery. Researchers will track cardiac regeneration in a novel reporter mouse model, combining high-resolution 3D imaging with functional analyses. By mapping regenerating cells and fibrotic areas, CardioReGen aims to unlock new insights into heart repair, paving the way for innovative treatments for heart failure.
Objective
During acute myocardial infarction (MI), up to 25% cardiomyocytes (CMs) in the left ventricle can die, which plays a major role in the progression to heart failure (HF). This loss is not compensated by new CM generation as, in adulthood, CMs lose their capability to proliferate. Recently, the host laboratory has proved that cardiac regeneration after MI can be stimulated by the therapeutic administration of various miRNAs in both mice (Eulalio et al., Nature, 2013) and pigs (Gabisonia et al., Nature, 2019). However, these studies also highlighted the safety issues related to the use of adeno-associated viruses for gene delivery.
Here, we want to design a novel therapeutic treatment to regenerate infarcted hearts based on the administration of selected pro-proliferative miRNAs delivered through lipid nanoparticles, which have been recently approved clinically for other conditions and offer an unprecedented translational possibility to stimulate cardiac regeneration. The effects of treatment will be comprehensively characterized, both functionally and structurally, at both cellular and organ levels, using a novel reporter mouse in which replicating cells become genetically labelled. We will monitor cardiac function and analyze the number of replicating CMs, as well as angiogenesis and molecular and cellular parameters related to HF. By taking advantage of my expertise, we will perform whole-organ, high-resolution 3D reconstructions of the regenerated hearts, employing cutting-edge optical imaging platforms (Olianti et al., PBMB, 2021). The spatial distribution and arrangement of proliferating CMs, connexins and fibrotic patches will be mapped and quantified in 3D. For each heart, structural information will be correlated to functional analyses.
The findings of this project will provide novel and important information on the molecular, functional and structural correlates of cardiac regeneration, which is essential to support therapeutic development in this field.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2024-PF-01
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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.
WC2R 2LS London
United Kingdom
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