Foundation for innovation
in Cardiometabolism and Nutrition

CAVD project: how to reconstitute in vitro mature contractile heart tissue?

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is the cardiomyopathy that accounts for one of the leading causes of sudden death in young patients under 40. It is characterized by massive inflammation of cardiac tissue, accompanied by progressive loss of muscle cells (cardiomyocytes), which are replaced by fibro-fatty infiltrates, leading to an increased risk of potentially fatal ventricular arrhythmias.

Led by Dr Pierre Bobin, the ARVC project aims to use artificial engineered heart tissues (EHTs), derived from human induced pluripotent stem cells, as a translational research tool that should, in the medium term, make it possible to test new approaches to treating ARVC.

What is the ARVC project?

The ARVC project aims to develop and improve the technology of artificial engineered heart tissues (better known by the acronym EHT for Engineered Heart Tissues) derived from human induced pluripotent stem cells (hiPSCs) in order to reconstitute in vitro a mature contractile heart tissue reproducing mechanical stress as observed in vivo and able to replicate cellular and structural ARVC phenotypes.

The project builds on encouraging preliminary results obtained during the first three years of developing EHT technology in the research unit led by Prof. Estelle Gandjbakhch and Dr Eric Villard. It relies on the creation of stem cell lines from blood samples taken from patients carrying genetic mutations associated with ARVC.

This project should therefore make it possible to develop a genetically adjustable human tissue model that enables not only observation and study of the tissue disorganization seen in the terminal stage, but above all the reproduction of ARVC progression throughout its multiple stages of development.

The innovative and unique nature of the project

The development of this model, currently unique in France, combined with the use of state-of-the-art techniques and technologies such as iPS cells coupled with genome editing techniques, should make it possible to study the pathological mechanisms induced by the two major mutations associated with ARVC within the patient’s genetic context.

This new strategy thus paves the way for using EHTs as a translational research tool that should, in the medium term, make it possible to test new approaches to treating ARVC such as gene therapy, with the goal of developing a personalized medical approach to genetic cardiac diseases.

Patronage in support of innovation

Crédit Agricole d’Ile-de-France Mécénat accepted to support this innovative research project in 2022 and thus joined the community of IHU ICAN patrons.

In this context, we were pleased to welcome their delegation for a presentation of the project by the dedicated research team: Prof. E. Gandjbakhch (Head of the Arrhythmology Unit, Institute of Cardiology, Pitié-Salpêtrière Hospital), Dr E. Villard (Scientific Lead), and Dr P. Bobin (Postdoctoral Researcher) in the Genomics and Pathophysiology of Myocardial Diseases team of UMRS 1166.

This meeting enabled the members of the delegation to discover the UMRS 1166 research laboratories as well as the cell culture laboratory where engineered heart tissues (EHTs) are developed, a model currently unique in France.

“The support of Crédit Agricole d’Ile-de-France Mécénat is important for the team; it will allow us to concretely accelerate our research work, which is very costly because it involves highly innovative techniques,” explains Pierre Bobin, a postdoctoral researcher in cardiovascular physiology.