Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction
Juan José Gavira (1), Emilio Nasarre (1), Gloria Abizanda (2), Maitane Pérez-Ilzarbe (2), Alba de Martino-Rodriguez (3), José A. García de Jalón (3), Manuel Mazo (2), Alfonso Macias (1), Ignacio García-Bolao (1), Beatriz Pelacho (2), Diego Martínez-Caro (1) and Felipe Prósper (2)
(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
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 10(6) 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 DeltaLVEF 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 DeltaLVEF 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.
Repeated injection of SkM in a model of chronic MI is feasible and safe and induces a significant improvement in cardiac function.
CITATION Eur Heart J. 2010 Apr;31(8):1013-2