Modeling heart disease with iPS-derived engineered heart tissue, part II

• Applicant: Professor Dr. Arne Hansen
• Subject Area: Pharmacology
• Term: from 2016 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 313744660

The concept of patient-specific human induced pluripotent stem cell-cardiomyocyte (hiPSC-CM) test models is highly attractive, but still in its infancy due to heterogeneity and immaturity of hiPSC-CM and lack of models to analyze physiological parameter like contractile force. The objective of this proposal is to further develop and apply a model for hiPSC-CM disease modeling with high predictivity based on contractile force. In the first project period, we showed that the engineered heart tissue (EHT) model is suitable to study functional consequences of gene mutations and that contractile force regulation in hiPSC-EHT replicates many aspects of human heart tissue. Pilot experiments indicate that hiPSC-EHTs promote mitochondrial maturation. Based on these findings we apply for a three year program to comprehensively study in hiPSC-EHTs (i) the status of mitochondrial and metabolic maturity, (ii) mechanisms of the autosomal recessive Primary Carnitine Deficiency (PCD) and (iii) the question, if PCD heterozygosity increases the risk for features of cardiac hypertrophy in an afterload enhancement model. The project will contribute to a better understanding of mechanisms of PCD and help unfolding the full potential of hiPSC for human disease modeling.

• DFG Programme: Research Grants
• Co-Investigator: Professor Dr. Thomas Eschenhagen