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Eur J Cardiothorac Surg 2007;31:444-451. doi:10.1016/j.ejcts.2006.12.023
Copyright © 2007, European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved

Non-cultured cell transplantation in an ovine model of non-ischemic heart failure

Nicolas Borenstein*, Valérie Chetboul, Patrick Bruneval, Mehrak Hekmati, Renaud Tissier, Luc Behr, Geneviève Derumeaux, Didier Montarras

IMM Recherche, 42 bd Jourdan, 75014 Paris, France

Received 26 May 2006; received in revised form 30 November 2006; accepted 4 December 2006.

* Corresponding author. Tel.: +33 1 56 61 68 21; fax: +33 1 56 61 67 40. (Email: nicolas.borenstein{at}imm.fr).

Objective: Cell therapy may be a promising alternative or adjunct to current treatment modalities for ischemic heart failure. But little is known on the impact of myogenic cell transplantation in large animal models of non-ischemic cardiomyopathy. The aim of the present study was to explore whether an ovine model of toxin-induced heart disease could benefit from non-cultured skeletal muscle cell transplantation. Methods: Sequential intracoronary injections of doxorubicin (0.75 mg/kg) were carried out every 2 weeks until echocardiographic detection of myocardial dysfunction. Sheep were then randomly assigned to either non-cultured cell transplantation (n = 8) or placebo injection (n = 5). For the cell therapy group, a skeletal muscle biopsy (about 10 g) was explanted from each animal approximately 3 h before grafting. After thoracotomy, 20 epicardial injections were carried out. The animals were assessed one last time before sacrifice, 2 months after the thoracotomy. Cells were tracked with cmDiI (red fluorescence) and characterized with immunohistochemistry with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. Results: Two months after intramyocardial grafting, tissue Doppler imaging and conventional echocardiographic assessment of the groups showed a marked improvement in the non-cultured cell therapy group. Ejection fraction (EF) (p < 0.05) as well as systolic endocardial velocities (p < 0.01) improved versus the placebo group. CmDiI and skeletal myosin heavy chain expression was detected in all animals at 2 months after implantation confirming engraftment of skeletal muscle cells. Conclusions: In conclusion, our data indicate that non-cultured muscle cell transplantation is feasible and may translate into a functional benefit in an ovine model of dilated heart failure.

Key Words: Cell transplantation • Cell culture • Satellite cells • Cardiomyopathy • Heart failure






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Copyright © 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier. All rights reserved.