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STEM CELL MODELS TO UNRAVEL THE SUSCEPTIBILITY AND RESILIENCE TO DEVELOP HEART FAILURE

Objective

The overarching objective of STOP-HF is to generate human induced pluripotent stem cells (hiPSC) derived cardiomyocytes from two specific forms of heart failure (HF) with a clear trigger to unravel common pathophysiological mechanisms involved in the early development of HF. The project is focused on two specific forms of HF, both with a clear trigger: pregnancy and anthracyclines.

Better understanding of early molecular pathways leading to HF and knowledge about inter-individual susceptibility is needed.
For detection of early changes on a molecular level cardiac tissue is needed.
Generation of patient specific cardiac cells from skin fibroblasts (hiPSC technology) is a novel and innovative approach.

SPECIFIC OBJECTIVES
1. Fabrication and maturation of 3D cardiac tissue from hiPS derived cardiomyocytes.
2. Generate and characterize hiPS derived cardiomyocytes and endothelial cells from females with pregnancy induced HF and unravel differences on transcriptome level.
3. Generate and characterize hiPSC derived cardiomyocytes from patients with high susceptibility and resilience to develop anthracycline-induced HF and compare them on transcriptome level.
4. Integrate the results for coding and non-coding RNAs from objective 1+2 and identify overlapping pathways.
5. Validate discoveries on transcriptome level in vitro, in vivo and apply for the development of HF in the general population.

WORKPACKAGES
WP1: Optimize fabrication and maturation of 3D cardiac tissue from hiPS derived cardiomyocytes
WP 2A:Validate the model and compare hiPS derived cardiomyocytes and endothelial cells from PPCM and healthy sisters on transcriptome level;
WP 2B:Validate the model and compare hiPS derived cardiomyocytes from both patients with high susceptibility and resilience to develop HF after anthracyclins on transcriptome level;
WP 3:Integration of transcriptome data from WP 2A+2B;
WP 4:Validation of novel pathways in vitro, in vivo and new onset HF in the general population.

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2016-STG

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Host institution

ACADEMISCH ZIEKENHUIS GRONINGEN
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.

€ 1 496 875,00
Address
HANZEPLEIN 1
9713 GZ Groningen
Netherlands

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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.

€ 1 496 875,00

Beneficiaries (1)

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