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European Heart Journal Advance Access published online on August 22, 2009
European Heart Journal, doi:10.1093/eurheartj/ehp342
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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

Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction

Juan José Gavira1, Emilio Nasarre1, Gloria Abizanda2, Maitane Pérez-Ilzarbe2, Alba de Martino-Rodriguez3, José A. García de Jalón3, Manuel Mazo2, Alfonso Macias1, Ignacio García-Bolao1, Beatriz Pelacho2, Diego Martínez-Caro1 and Felipe Prósper2,*

1 Department of Cardiology and Cardiovascular Surgery, University of Navarra, Pamplona, Spain
2 Spain and Foundation for Applied Medical Research, Division of Cancer, Hematology and Cell Therapy, University of Navarra, Av Pio XII 36, Pamplona 31008, Spain
3 Department of Animal Pathology, Veterinary Faculty, University of Zaragoza, Zaragoza, Spain

Received 8 February 2009; revised 7 July 2009; accepted 4 August 2009 * Corresponding author. Tel: +34 948 255400, Fax: +34 948 255400, Email: fprosper{at}unav.es

Aims: Although transplantation of skeletal myoblast (SkM) in models of chronic myocardial infarction (MI) induces an improvement in cardiac function, the limited engraftment remains a major limitation. We analyse in a pre-clinical model whether the sequential transplantation of autologous SkM by percutaneous delivery was associated with increased cell engraftment and functional benefit.

Methods and results: Chronically infarcted Goettingen minipigs (n = 20) were divided in four groups that received either media control or one, two, or three doses of SkM (mean of 329.6 x 106 cells per dose) at intervals of 6 weeks and were followed for a total of 7 months. At the time of sacrifice, cardiac function was significantly better in animals treated with SkM in comparison with the control group. A significantly greater increase in the {Delta}LVEF was detected in animals that received three doses vs. a single dose of SkM. A correlation between the total number of transplanted cells and the improvement in LVEF and {Delta}LVEF was found (P < 0.05). Skeletal myoblast transplant was associated with an increase in tissue vasculogenesis and decreased fibrosis (collagen vascular fraction) and these effects were greater in animals receiving three doses of cells.

Conclusion: Repeated injection of SkM in a model of chronic MI is feasible and safe and induces a significant improvement in cardiac function.

Key Words: Stem cells • Myoblast • Myocardial infarction • Animal model • Swine


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