Copyright © 2006, European Society of Cardiology
A comparison between percutaneous and surgical transplantation of autologous skeletal myoblasts in a swine model of chronic myocardial infarction
aDepartment of Cardiology and Cardiovascular Surgery, University of Navarra, Spain
bHematology and Cell Therapy, University of Navarra, Spain
cDepartment of Pathology, Clínica Universitaria, University of Navarra, Spain
dFoundation for Applied Medical Research, Division of Cancer and Division of Physiology, University of Navarra, Spain
eDepartament of Animal Pathology, Veterinary Faculty, University of Zaragoza, Spain
* Corresponding author. Hematology and Cell Therapy, Clínica Universitaria, Avda. Pío XII 36, Pamplona 31008, Spain. Tel.: +34 948 255400; fax: +34 948 296500. Email address: fprosper{at}unav.es
Objective: Our aim was to compare the efficacy of surgical versus percutaneous administration of skeletal myoblasts (SkM) in a swine model of chronic myocardial infarction and to determine the mechanism(s) involved in their beneficial effect.
Methods Two months after induction of myocardial infarction (MI), Goettingen miniature pigs underwent autologous SkM transplant either by direct surgical injection (n=6) or percutaneous access and intramyocardial delivery under fluoroscopic and echocardiographic guidance (n=6). Control animals received media alone (n=4). Functional analysis was performed by 2D echocardiography. Myoblast engraftment, in vivo cell differentiation, vessel formation, fibrosis, and the ratio between collagen type I/III deposition were analyzed in the infarct (IA) and non-infarct area (NIA) by immunohistochemistry.
Results: Animals received a median of 407.55±115x106 BrdU-labeled autologous SkM. Myoblast transplant was associated with a statistically significant increase in left ventricular ejection fraction (p<0.01), increased vasculogenesis and decreased fibrosis (p<0.05), and reduced collagen type I/III ratio in the IA and NIA areas as compared with control animals. No differences were found between groups receiving SkM by percutaneous or surgical access.
Conclusions: Our results indicate that increased vasculogenesis and changes in matrix remodeling with decreased fibrosis are associated with the beneficial effect of SkM transplant in chronic MI. The equivalent benefit observed from surgical and percutaneous delivery has important clinical implications.
KEYWORDS Skeletal myoblasts; Myocardial infarction; Vasculogenesis; Fibrosis; Cell therapy
1 JJG and MPI contributed equally to this study and should be considered equal first authors.
Supported in part by grants from Fondo de Investigaciones Sanitarias PI042125, Ministerio de Ciencia y Tecnologia SAF2002-04575-C02-02, Sociedad Española de Cardiología, FEDER (INTERREG IIIA) and PIUNA. This project was funded in part through the "UTE project CIMA".
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