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Selection of human iPSC derived cardiomyocytes by sinGle cell geNe expression an...

Selection of human iPSC derived cardiomyocytes by sinGle cell geNe expression and pAtch clamp for a maTUre caRdiac modEl The incidence of cardiac arrhythmias in Europe is increasing because of aging and unexpected side effects of drugs, such as chemotherapeutics. To understand mechanisms underlying these conditions requires reliable preferably human... ver más

31/01/2022

Leiden University...

188K€

Presupuesto del proyecto: 188K€

Líder del proyecto

ACADEMISCH ZIEKENHUIS LEIDEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2022-01-31

MSCA-IF-2018: Individual Fellowships Objective:The goal of the Individual Fellowships is to enhance the creative and innovative potential...

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Este proyecto no cuenta con búsquedas de partenariado abiertas en este momento.

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1 Participantes

Leiden University Medical Ce...

187.57K€ | Lider

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Duración del proyecto: 33 meses Fecha Inicio: 2019-04-25
Fecha Fin: 2022-01-31

Líder del proyecto

ACADEMISCH ZIEKENHUIS LEIDEN No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 188K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto The incidence of cardiac arrhythmias in Europe is increasing because of aging and unexpected side effects of drugs, such as chemotherapeutics. To understand mechanisms underlying these conditions requires reliable preferably human models. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are presently good candidates since they share the genome of the individual from whom they are derived and can thus recapitulate genetic, ethnic and gender contributions to the cardiac disease phenotypes. However, their immature state and high inter- and intra-line variability is limiting their value as preclinical models. In the proposed project, I will address these issues through an interdisciplinary approach combining a unique 3D culture maturation system developed in my host lab with my expertise in electrophysiology. I will characterize gene expression and electrical properties of single cardiomyocytes simultaneously with view to directly correlating genes with function and identify molecular markers associated with the functionally mature cardiac phenotype. Two genetic cardiac diseases (one caused by an imprinted gene, the other by a postnatally expressed splice variant) for which the host already has hiPSC lines, will be used as proof of concept that hiPSC-CM maturation in this system is sufficient (i) to reveal disease phenotypes not evident in conventional culture and (ii) to identify molecular markers suitable for selecting mature hiPSC-CMs for drug testing. Overall, this project will provide the first functionally-relevant gene signature of (mature) hiPSC-CMs, and thus be an important advance in modelling all cardiomyocyte autonomous cardiac diseases more precisely for (personalized) drug screening. The outcome will be available to academic and private researchers to enhance rates of drug discovery and safety, and promote hiPSC-CMs as validated adult cardiac models to replace, at least in part, the use of animal models.

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