Assessing cardiac Contractility and Quantification of Underlying mechanisms In vitro via Response in Excitation-contraction coupling
|Assessing cardiac Contractility and Quantification of Underlying mechanisms In vitro via Response in Excitation-contraction coupling
|European Research Council - Proof of Concept (ERC-PoC)
|Leiden University Medical Center
Associated cell lines
Academia and industry urgently needs reliable models to study heart failure and toxic effects of drugs on the heart. While new models based on human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are now emerging, accurate readouts of cardiomyocyte function fall short of needs. Apart from improving the models biologically, more sensitive, informative and accurate readouts are needed to detect abnormal cardiomyocyte behaviour. Several tools have proven their ability to assess electrical changes or calcium handling in hiPSC-CMs, but they are typically incompatible with 3D tissue models and moreover, there is paucity of appropriate tools to quantify the most important function of myocardium: contraction. Our ERC Advanced Grant STEMCARDIOVASC entailed the development of improved tools for cardiac functionality. One of the most important bioassays developed as an outcome of STEMCARDIOVASC was the Triple Transient Measurement (TTM) System. The TTM System quantifies electrical activity, intracellular calcium flux and contractility simultaneously and is our answer to the challenge of pharma in understanding when and how drugs or diseases affect cardiac contractility using hiPSC-CM models. In this ERC Proof of Concept project “ACQUIRE”, we strive to bring the TTM to a commercial applicable service, and later product. To reach this goal we have set out four aims to come to a Minimum Viable Product: i) increase the flexibility of the system to accommodate a larger variety of optical probes, ii) increase the throughput of the system to compete with current measurement systems, iii) increase user friendliness by integrating software modules for running and analysing measurements and iv) define a route for commercialisation. Resulting from "ACQUIRE" the TTM System can be commercialized as a human cardiac based 3-in-1 assay for cardiotoxicity testing and a novel tool for providing mechanistic insight in the EC coupling for disease modelling and drug discovery.