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Cardiovascular Research Advance Access [Accepted Manuscript] published online on June 8, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp167
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Adipose-derived cardiomyogenic cells: in vitro expansion and functional improvement in a mouse model of myocardial infarction

Bertrand Léobon1, Jérôme Roncalli2,*, Carine Joffre1,*, Manuel Mazo4, Marie Boisson1, Corinne Barreau1, Denis Calise, Emmanuelle Arnaud1, Mireille André1, Michel Pucéat3, Luc Pénicaud1, Felipe Prosper4, Valérie Planat-Bénard1 and Louis Casteilla1

1 From UMR 5241 CNRS UPS, CHU Rangueil, 31054 Toulouse, France
2 Department of cardiology, CHU Rangueil, 31059 Toulouse cedex 9, France
3 UMR-861 INSERM/Université-Evry, I-Stem/AFM, 91030 Evry, France
4 Hematology and Cell Therapy and Foundation for Applied Medical Research, Division of Cancer, University of Navarra, Spain

Correspondence to L. Casteilla; tel: +33 5 62 17 08 91, Fax: +33 5 62 17 09 05, E-mail: casteil{at}toulouse.inserm.fr

Aims: Cells derived from the stroma vascular fraction (SVF) of mouse adipose tissue can spontaneously give rise to rare, functional, cardiac-like cells in vitro. This study aimed to improve the production of adipose-derived cardiomyogenic cells (AD-CMG), to characterize them and to assess their cardiac fate and functional outcomes after their administration in a mouse model of acute myocardial infarction.

Methods and results: The culture process optimized to improve in vitro cardiac specification consisted of a primary culture of murine SVF cells in semi-solid methylcellulose medium, a selection of AD-CMG cell clusters, and a secondary culture and expansion in BHK21 medium. AD-CMG cells were CD29+; CD31–, CD34–, CD44+, CD45–, CD81+, CD90–, CD117– and Flk-1– and expressed several cardiac contractile proteins. One, 2 and 4 weeks after their injection in mice having acute myocardial infarction, a strong presence of green fluorescent protein-positive cells was identified by immunohistochemistry as well as quantitative PCR. Echocardiography showed a significant reduction of remodelling and stability of left ventricle ejection fraction in the AD-CMG cell-treated group versus controls. Vascular density analysis revealed that AD-CMG administration was also associated with stimulation of angiogenesis in peri-infarct areas.

Conclusion: Cardiomyogenic cells can be selected and expanded in large amount from mouse adipose tissue. They can survive and differentiate in an acute myocardial infarction model, avoiding remodelling and impairment of cardiac function, and can promote neo-vascularization in the ischemic heart.

KEYWORDS adipose-derived stem cells; cardiomyocyte; acute myocardial infarction; ischemia; cell therapy

Time for primary review: 34 Days

* Jérôme Roncalli and Carine Joffre contributed equally to this work.


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