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Assessing cardiac Contractility and Quantification of Underlying mechanisms In vitro via Response in Excitation-contraction coupling

Periodic Reporting for period 1 - ACQUIRE (Assessing cardiac Contractility and Quantification of Underlying mechanisms In vitro via Response in Excitation-contraction coupling)

Berichtszeitraum: 2020-09-01 bis 2022-08-31

Academia and industry urgently need reliable models to study heart failure and toxic effects of drugs on the heart as conventional laboratory animal tests do not always detect risk. 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 endeavoured to bring the TTM to a commercially applicable service, and later product. Our project was successful, but it turned out differently than expected. Whilst we anticipated considerable work would be needed to attract end-users, two industrial technology companies actually expressed high interest in the system in an early phase of our project. Currently, we are investigating whether we can transfer (parts of) our technologies developed in the TTM system to their existing assay platforms.