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J Thorac Cardiovasc Surg 2005;129:1119-1127
© 2005 The American Association for Thoracic Surgery

Surgery for Congenital Heart Disease

Noncultured cell transplantation in an ovine model of right ventricular preparation

^a IMM Recherche, Centre d’Expérimentation et de Recherche Appliquée, Paris
^b Cardiac Surgery Department, Rui Jin Hospital, Shanghai, China
^c Service d’Anatomie Pathologique, Institut Mutualiste Montsouris, Paris
^d Département de Pathologie Cardiaque, Institut Mutualiste Montsouris, Paris
^e Laboratoire d’Anatomie Pathologique, Hôpital Européen Georges Pompidou, Paris
^f Unité de Génétique Moléculaire du Développement, Institut Pasteur, Paris, France

Received for publication May 21, 2004; revisions received September 3, 2004; accepted for publication September 20, 2004.

^_* Address for reprints: Nicolas Borenstein, IMM Recherche, 42 boulevard Jourdan, 75014 Paris, France (E-mail: nicolas.borenstein{at}imm.fr).

OBJECTIVE: Beyond the first 2 months of life, pulmonary artery banding is warranted before two-stage arterial switch operation. The aim of this study was to explore whether myogenic cell transplantation could contribute to right ventricular function during pulmonary artery constriction in an ovine model.

METHODS: Sixteen rams were assigned to one of the following groups: group 1, simple pulmonary artery banding (n = 5); group 2, pulmonary artery banding and cell implantation in the right ventricle (n = 7); and group 3, pulmonary artery banding and placebo injection in the right ventricle (n = 4). Hemodynamic assessment with pressure-volume loops was performed on days 0 and 60. The pulmonary artery banding and the injections were achieved through a left fourth intercostal thoracotomy. Autologous myogenic cell implantation was carried out with a noncultured cell preparation, as previously described by our group. Implanted sites were processed with monoclonal antibodies to a fast skeletal-specific isoform of myosin heavy chain (MY32).

RESULTS: Skeletal myosin heavy chain expression was detected at 2 months after noncultured cell implantation in all grafted animals. Right ventricular training resulted in statistically significant increased signs of contractility in all three groups. There was no observed difference, however, between the cell therapy group and the other two groups with respect to signs of cardiac function.

CONCLUSION: Successful engraftment of noncultured cells into right ventricular myocardium did not translate into a functional benefit that we could demonstrate in our ovine model. Cellular therapy thus is probably not useful to strengthen a left ventricle being retrained through pulmonary artery banding before arterial switch operation. However, cell transplantation may affect the outcome of right ventricular failure long term after atrial switch operation. Although preliminary, this investigation paves the way for further research into cellular cardiomyoplasty, right ventricular failure, and congenital heart disease.

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