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

Description du projet

Un test 3 en 1 pour tester la cardiotoxicité

Les cellules souches pluripotentes induites par l’homme (CSPi) ont révolutionné le développement de modèles in vitro d’organes et de maladies. Elles ont simultanément souligné la nécessité de lectures plus sensibles, informatives et précises du comportement spécifique aux cellules et de la fonction anormale. Le projet ACQUIRE, financé par l’UE, se concentre sur les outils permettant d’évaluer la fonctionnalité des cardiomyocytes humains dérivés des CSPi. L’objectif principal est de mettre sur le marché le système de mesure transitoire triple (TTM) précédemment développé. Le système TTM quantifie simultanément l’activité électrique, le flux de calcium intracellulaire et la contractilité, offrant un outil multimodal pour l’évaluation in vitro de la toxicité des médicaments sur des modèles de cardiomyocytes humains dérivés de CSPi.

Objectif

"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."

Régime de financement

ERC-POC - Proof of Concept Grant

Institution d’accueil

ACADEMISCH ZIEKENHUIS LEIDEN
Contribution nette de l'UE
€ 150 000,00
Adresse
ALBINUSDREEF 2
2333 ZA Leiden
Pays-Bas

Voir sur la carte

Région
West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
Aucune donnée

Bénéficiaires (1)