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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.

Host institution

ACADEMISCH ZIEKENHUIS GRONINGEN
Net EU contribution
€ 1 496 875,00
Address
Hanzeplein 1
9713 GZ Groningen
Netherlands

See on map

Region
Noord-Nederland Groningen Overig Groningen
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00

Beneficiaries (1)

ACADEMISCH ZIEKENHUIS GRONINGEN
Netherlands
Net EU contribution
€ 1 496 875,00
Address
Hanzeplein 1
9713 GZ Groningen

See on map

Region
Noord-Nederland Groningen Overig Groningen
Activity type
Higher or Secondary Education Establishments
Other funding
€ 0,00