High throughput screening system for cardiac drugs

The HeartCHIP II project will develop a novel automated high-throughput (HT) drug screening system to identify promising candidates. The system will uniquely use functional video microscopy of heart tissue cultures as a read-out parameter. Previous research by the project partners has shown that this provides a very promising non-destructive method for long-term monitoring of in vitro systems, which is suitable for automation.

Heart failure (HF) is a serious disease that afflicts ~2-3% of the population. HF is mainly caused by other (cardiovascular) disorders such as a previous myocardial infarction or hypertension. Although basic research into more effective drugs against HF is ongoing, there is a lack in drug-development, in part because of a lack of suitable pre-clinical tests to identify promising drug candidates.

In order to develop the prototype HeartCHIP II system, the consortium partners will first study the constituent parts of the planned method: 1) an organ-on-chip (OOC) culture method for human induced pluripotent stem cell (hiPSC) derived multi-cell (cardiomyocyte, endothelial and fibroblast) 3D cultures, 2) dedicated software for functional video microscopy analysis of read-out parameters and 3) disease modelling using hiPSC-derived cardiomyocytes with disease-specific mutations. At the end of the project, the prototype system will be validated using various types of stimuli with known effect, e.g. pharmaceutical drugs, culture substrates with varying stiffness, genetic mutations with known effects. The results of this project will show proof-of-concept for the HeartCHIP II system as a pre-clinical test to identify promising drug candidates.

Following further technical and analytical validation of the HeartCHIP II system, the system will be commercialised by out-licensing and offering pre-clinical drug screening to biotech and pharmaceutical companies in the cardiovascular field.