title: Treatment of reperfused ischemia with adipose-derived stem cells in a preclinical Swine model of myocardial infarction.
abstract: The aim of the study was to determine the long-term effect of transplantation of adipose-derived stromal cells (ADSCs) in a preclinical model of ischemia/reperfusion (I/R). I/R was induced in 28 Goettingen minipigs by 120 min of coronary artery occlusion followed by reperfusion. Nine  days later, surviving animals were allocated to receive transendocardial injection of a mean of 213.6 ± 41.78 million green fluorescent protein (GFP)-expressing ADSCs (n = 7) or culture medium as control (n = 9). Heart function, cell engraftment, and histological analysis  were performed 3 months after transplantation. Transplantation of ADSCs induced a statistically significant long-lasting (3 months) improvement in cardiac function and geometry in comparison with control animals. Functional improvement was associated with an increase in angiogenesis and vasculogenesis  and a positive effect on heart remodeling with a decrease in fibrosis and cardiac hypertrophy in animals treated with ADSCs. Despite the lack of cell engraftment after 3 months, ADSC transplantation induced changes in the ratio between MMP/TIMP. Our results indicate that transplantation of  ADSCs, despite the lack of long-term significant cell engraftment, increases vessel density and prevents adverse remodeling in a clinically relevant model of myocardial infarction, strongly suggesting a paracrine-mediated effect. ADSCs thus constitute an attractive candidate for the treatment  of myocardial infarction.
authors.affiliation: Hematology and Cell Therapy, Clinica Universidad de Navarra, Pamplona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mazo
authors.forename: Salomón
authors.initials: S
authors.lastname: Hernández
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Gavira
authors.forename: Gloria
authors.initials: G
authors.lastname: Abizanda
authors.forename: Miriam
authors.initials: M
authors.lastname: Araña
authors.forename: Tania
authors.initials: T
authors.lastname: López-Martínez
authors.forename: Cristina
authors.initials: C
authors.lastname: Moreno
authors.forename: Juana
authors.initials: J
authors.lastname: Merino
authors.forename: Alba
authors.initials: A
authors.lastname: Martino-Rodríguez
authors.forename: Alicia
authors.initials: A
authors.lastname: Uixeira
authors.forename: José A
authors.initials: JA
authors.lastname: García de Jalón
authors.forename: Juan
authors.initials: J
authors.lastname: Pastrana
authors.forename: Diego
authors.initials: D
authors.lastname: Martínez-Caro
authors.forename: Felipe
authors.initials: F
authors.lastname: Prósper
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D003331:Coronary Vessels / Q000502:physiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism; D009389:Neovascularization, Pathologic; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013552:Swine; D013556:Swine, Miniature; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases