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(Circulation. 2003;107:3088.)
© 2003 American Heart Association, Inc.

Basic Science Reports

Noncultured, Autologous, Skeletal Muscle Cells Can Successfully Engraft Into Ovine Myocardium

Nicolas Borenstein, DVM, MSc; Patrick Bruneval, MD; Mehrak Hekmati, PhD; Christophe Bovin;; Luc Behr, DVM; Christian Pinset, MD; François Laborde, MD; Didier Montarras, PhD

From the IMM Recherche, Institut Mutualiste Montosuris (N.B., M.H., L.B., F.L.); the Laboratoire d’Anatomie Pathologique, Hôpital Européen Georges Pompidou (P.B.); the Département d’Anatomie Pathologique, Institut Mutualiste Montsouris (C.B.); CELOGOS (C.P.); and the Unité de Génétique Moléculaire du Développement (D.M.), Institut Pasteur, Paris France.

Correspondence to Nicolas Borenstein, IMM Recherche, 42 bd Jourdan, 75014 Paris, France (e-mail cera{at}imm.fr), or Didier Montarras, Unité de Génétique Moléculaire du Développement, Institut Pasteur, 28 rue du Docteur-Roux, 75724 Paris Cedex 15, France (e-mail dmontarr@pasteur.fr).

Background— There is compelling evidence showing that cellular cardiomyoplasty can improve cardiac function. Considering the potential benefit of using noncultured muscle cells (little time, lower cost, reduced risk of contamination), we investigated the feasibility of grafting cells obtained directly after enzymatic dissociation of skeletal muscle biopsies into ovine myocardium. We hypothesized that those noncultured muscle cells would engraft massively.

Methods and Results— Autologous, intramyocardial skeletal muscle cell implantation was performed in 8 sheep. A skeletal muscle biopsy sample (10 g) was explanted from each animal. The sheep were left to recover for 3 hours and reanesthetized when the cells were ready for implantation. A left fifth intercostal thoracotomy was performed, and 10 epicardial injections of the muscle preparation (between 10 and 20 million cells) were carried out. All sheep were euthanized 3 weeks after myocardial implantation. Immunohistochemistry was performed with monoclonal antibodies to a fast skeletal isoform of myosin heavy chain. Skeletal myosin heavy-chain expression was detected in all slides at 3 weeks after implantation in 8 of 8 animals, confirming engraftment of skeletal muscle cells. Massive areas of engraftment (from 2 to 9 mm in diameter) or discrete loci were noted within the myocardial wall.

Conclusions— Our results indicate that noncultured skeletal muscle cells can successfully and massively engraft in ovine myocardium. Thus, avoiding the cell culture expansion phase is feasible and could become a promising option for cellular cardiomyoplasty.

Key Words: heart • cells • transplantation • infarction • muscles

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