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© Research
Publication : European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery - 12 Jan 2007

Borenstein N, Chetboul V, Bruneval P, Hekmati M, Tissier R, Behr L, Derumeaux G, Montarras D

Link to Pubmed [PMID] – 17223566

Eur J Cardiothorac Surg 2007 Mar;31(3):444-51

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 3h 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.

http://www.ncbi.nlm.nih.gov/pubmed/17223566