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


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.


CONCLUSIONS
Repeated injection of SkM in a model of chronic MI is feasible and safe and induces a significant improvement in cardiac function.
Gavira
Juan José
JJ
Department of Cardiology and Cardiovascular Surgery, University of Navarra, Pamplona, Spain.
Nasarre
Emilio
E
Abizanda
Gloria
G
Pérez-Ilzarbe
Maitane
M
de Martino-Rodriguez
Alba
A
García de Jalón
José A
JA
Mazo
Manuel
M
Macias
Alfonso
A
García-Bolao
Ignacio
I
Pelacho
Beatriz
B
Martínez-Caro
Diego
D
Prósper
Felipe
F
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology; D002454:Cell Differentiation; D002908:Chronic Disease; D005355:Fibrosis; D006085:Graft Survival; D007150:Immunohistochemistry; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature; D018487:Ventricular Dysfunction, Left / Q000209:etiology; D020257:Ventricular Remodeling / Q000502:physiology