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Human mini hearts: looking for culprits and victims in cardiac disease

Project description

Models of cardiac conditions

Heart diseases, including arrhythmia, are often silent until a patient experiences certain symptoms such as chest pain and discomfort. Being able to predict heart conditions and prevent cardiac failure is of paramount importance, but currently, we lack the necessary models to study the pathophysiological mechanisms. The EU-funded Mini-HEART project proposes to generate cardiac microtissues using human induced pluripotent stem cells (hiPSCs) differentiated to cardiac cells in vitro. Researchers will recapitulate cardiac disease in these hiPSC models and decipher the role of different cell types in cardiac phenotype. Moreover, they will test new therapeutic approaches for heart disease.

Objective

Cardiac disease causes morbidity and mortality as frequently as cancer. Predicting cardiac arrhythmia and cardiac failure, understanding multicellular (patho)physiological mechanisms, and devising new treatments represent unmet needs in the field. Human induced pluripotent stem cells (hiPSC) could revolutionise the way we study human disease but unfortunately, they still fall short in recapitulating variable phenotypes and complex cardiovascular diseases. This is partly due to functional immaturity of hiPSC-derived cardiac tissues, shortage of methods for accurate functional analysis and inability to identify cell-type specific contributions to disease pathology. I will address these challenges in Mini-HEART. We recently assembled novel three-dimensional multi-cellular cardiac microtissues as an important step towards full maturation and used these to demonstrate that cardiac disease mutations might directly affect non-myocyte cardiac cells. However, application of hiPSC microtissues to precision medicine remains to emerge. Using a multidisciplinary approach, I will combine isogenic hiPSC, their differentiation into distinct cell types of the heart, multifaceted biophysical assays, and tissue engineering to prove cell-type causality of disease and identify new molecules targeting the culprit cells to rescue the disease phenotype. I plan to use our unique complex hiPSC-cardiac microtissue to 1) identify and synthetically enhance maturation mechanisms; 2) reveal late arrhythmic and fibrotic phenotypes; 3) dissect cell-type specific contributions to complex cardiac diseases, including the role of macrophages and sympathetic nerves; 4) test two therapeutic strategies based on drug-tailoring and gene editing, to modulate the disease phenotype. Together, Mini-HEART will create new opportunities for designing novel biomedical tools to i) capture phenotypic changes, ii) reveal (patho)physiological mechanisms and ii) develop new therapeutic approaches for heart disease.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-COG - Consolidator Grant

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Call for proposal

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(opens in new window) ERC-2020-COG

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Host institution

UNIVERSITA DEGLI STUDI DI PADOVA
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.

€ 1 500 000,00
Address
VIA 8 FEBBRAIO 2
35122 PADOVA
Italy

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Region
Nord-Est Veneto Padova
Activity type
Higher or Secondary Education Establishments
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Total cost

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.

€ 1 500 000,00

Beneficiaries (2)

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