Project description
Could we lower oxygen levels in the heart to treat a heart attack?
Myocardial infarction (MI) or heart attack is caused by a blockage in the blood flow to the heart. MI leads to cardiac tissue scarring and dysfunction that cannot be repaired through endogenous tissue regeneration. The EU-funded PhyCaR project will investigate the hypothesis that lowering the oxygen levels (hypoxia) in cardiac tissue may promote the differentiation of heart progenitor cells and induce repair. Researchers will employ an animal model of MI to transplant a scaffold loaded with heart progenitor cells and a chemical that causes hypoxia. PhyCaR will evaluate the impact of hypoxia on heart regeneration and identify the implicated mechanisms.
Objective
Ischemic heart disease is the main cause of death in Europe and the world, and its main manifestation is myocardial infarction (MI). The MI leads to loss of heart tissue, tissue scarring associated with fibrosis, dysfunction and heart failure. The pathophysiological basis of heart failure in humans lies in the heart's inability to regenerate. Adult cardiomyocytes (CMs) perform mitosis after MI, but their proliferation rate is extremely low for restoring normal cardiac function. During development, low levels of intrauterine oxygen promote the proliferation of CMs, which decreases postpartum due to the metabolic adaptation that implies exposure to atmospheric oxygen. Induced hypoxia in adult mammals promotes proliferation of CMs, and is required for cardiac regeneration (CR) of teleost such as zebrafish. However, the mechanisms that mediate these effects are unclear. Systemic exposure to hypoxia has been proposed as a strategy to promote CR; however, its adverse effects on other vital organs limit its clinical use. Here, we have proposed the generation of a temporary and localized hypoxia in the infarcted area of the heart. To achieve this, we will synthesize fibrin scaffolds bearing FG-4592 - an agent that mimics the effects of hypoxia (pseudohypoxia) - using bioprinting 3D. Besides, scaffolds will be loaded with CMs derived from Induced pluripotent stem cells (iPSCs-CMs), and will be implanted in MI models of pigs. Delivery of FG-4592 and iPSCs-CMs through scaffolds in the damaged myocardium would promote proliferation of resident CMs and cell turnover, respectively. Additionally, we will explore two mechanisms by which hypoxia could promote CR, remodeling of the extracellular matrix and angiogenesis mediated by angiopoietin-like 4 (Angptl-4). This project is a necessary effort to materialize the latest advances in hypoxia and CR by combining cell therapy with a cutting-edge technology in the tissue engineering field, 3D bioprinting.
Fields of science (EuroSciVoc)
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.
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.
- medical and health sciences medical biotechnology tissue engineering
- medical and health sciences medical biotechnology cells technologies stem cells
- medical and health sciences clinical medicine obstetrics postnatal care
- natural sciences biological sciences zoology mammalogy
- medical and health sciences clinical medicine cardiology
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Keywords
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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2020
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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.
08908 L'Hospitalet De Llobregat
Spain
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.