Objective Heart failure (HF) is the common end-stage of different medical conditions. It is the only growing cardiovascular disease and its prognosis remains worse than that of many malignancies. The lack of evidence-based treatment for patients with diastolic HF (HFpEF) exemplifies that the current “one for all” therapy has to be advanced by an individualized approach. Inherited cardiomyopathies can serve as paradigmatic examples of different HF pathogenesis. Both gain- and loss-of-function mutations of the same gene cause disease, calling for disease-specific agonism or antagonism of this gene´s function. However, mutations alone do not predict the severity of cardiomyopathies nor therapy, because their impact on cardiac myocyte function is modified by numerous factors, including the genetic context. Today, patient-specific cardiac myocytes can be evaluated by the induced pluripotent stem cell (hiPSC) technology. Yet, unfolding the true potential of this technology requires robust, quantitative, high content assays. Our recently developed method to generate 3D-engineered heart tissue (EHT) from hiPSC provide an automated, high content analysis of heart muscle function and the response to stressors in the dish. The aim of this project is to make the technology a clinically applicable test. Major steps are (i) in depths clinical phenotyping and genotyping of patients with cardiomyopathies or HFpEF, (ii) follow-up of the clinical course, (iii) generation of hiPSC lines (40 patients, 40 healthy controls), and (iv) quantitative assessment of hiPSC-EHT function under basal conditions and in response to pro-arrhythmic or cardio-active drugs and chronic afterload enhancement. The product of this study is an SOP-based assay with standard values for hiPSC-EHT function/stress responses from healthy volunteers and patients with different heart diseases. The project could change clinical practice and be a step towards individualized risk prediction and therapy of HF. Fields of science medical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesclinical medicinecardiologycardiovascular diseases Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-AG-LS7 - ERC Advanced Grant - Diagnostic tools, therapies and public health Call for proposal ERC-2013-ADG See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF EU contribution € 2 494 728,00 Address Martinistrasse 52 20251 Hamburg Germany See on map Region Hamburg Hamburg Hamburg Activity type Higher or Secondary Education Establishments Administrative Contact Frank Neumann (Mr.) Principal investigator Thomas Hans Eschenhagen (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF Germany EU contribution € 2 494 728,00 Address Martinistrasse 52 20251 Hamburg See on map Region Hamburg Hamburg Hamburg Activity type Higher or Secondary Education Establishments Administrative Contact Frank Neumann (Mr.) Principal investigator Thomas Hans Eschenhagen (Prof.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
