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Cardiovascular Research Advance Access [Accepted Manuscript] published online on November 3, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn299
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org.

An in vitro beating heart model for long term assessment of experimental therapeutics

Walter Habeler, Séverine Pouillot, Alexandra Plancheron, Michel Pucéat, Marc Peschanski and Christelle Monville*

INSERM/UEVE UMR 861, I-STEM, AFM, 5 rue Henri Desbruères, Evry 91030 cedex, France

* Corresponding author: Christelle Monville, INSERM/UEVE UMR 861, I-STEM, AFM, 5 rue Henri Desbruères, Evry 91030 cedex, France, Tel: +33169908528, Fax: +33169908521, E-mail: cmonville{at}istem.genethon.fr

Aim: Within the framework of studies aiming at regenerative medicine for cardiovascular disease, we have developed an in vitro model to analyse human embryonic stem cell engraftment into the myocardium.

Methods and results: This model is based on organotypic rat ventricular slices maintained in culture at the air-medium interface on semiporous membranes. Survival and differentiation of human cardiomyocytes derived from embryonic stem cells were then assessed for several months. In addition, we observed that ventricular tissue slices not only exhibited normal histology, but also rhythmic contractions till the end of the experiments (up to 3 months). Similar results were obtained using ventricular slices obtained from two human foetuses at 8 and 9.5 weeks of age. Calcium transients were associated to the beating frequency, and the pattern was modulated in a dose-dependent manner by epinephrine.

Conclusion: Our data suggest that the organotypic heart slice culture on semiporous membranes is a relevant in vitro heart model for long term histological and physiological studies.

Time for primary review: 28 Days


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