Adipose stromal vascular fraction improves cardiac function in chronic myocardial infarction through differentiation and paracrine activity.
Fresh adipose-derived cells have been shown to be effective in the treatment of acute myocardial infarction (MI), but their role in the chronic setting is unknown. We sought to determine the long-term effect of the adipose derived-stromal vascular fraction (SVF) cell transplantation  in a rat model of chronic MI. MI was induced in 82 rats by permanent coronary artery ligation and 5 weeks later rats were allocated to receive an intramyocardial injection of 10(7) GFP-expressing fresh SVF cells or culture media as control. Heart function and tissue metabolism were  determined by echocardiography and (18)F-FDG-microPET, respectively, and histological studies were performed for up to 3 months after transplantation. SVF induced a statistically significant long-lasting (3 months) improvement in cardiac function and tissue metabolism that was associated  with increased revascularization and positive heart remodeling, with a significantly smaller infarct size, thicker infarct wall, lower scar fibrosis, and lower cardiac hypertrophy. Importantly, injected cells engrafted and were detected in the treated hearts for at least 3 months, directly  contributing to the vasculature and myofibroblasts and at negligible levels to cardiomyocytes. Furthermore, SVF release of angiogenic (VEGF and HGF) and proinflammatory (MCP-1) cytokines, as well as TIMP1 and TIMP4, was demonstrated in vitro and in vivo, strongly suggesting that they have  a trophic effect. These results show the potential of SVF to contribute to the regeneration of ischemic tissue and to provide a long-term functional benefit in a rat model of chronic MI, by both direct and indirect mechanisms.
Hematology and Cell Therapy and Foundation for Applied Medical Research, Division of Cancer, Clínica Universitaria, University of Navarra, Navarra, Spain.
Manuel
M
Mazo
Arantxa
A
Cemborain
Juan José
JJ
Gavira
Gloria
G
Abizanda
Miriam
M
Araña
Mayte
M
Casado
Mario
M
Soriano
Salomón
S
Hernández
Cristina
C
Moreno
Margarita
M
Ecay
Edurne
E
Albiasu
Miriam
M
Belzunce
Josune
J
Orbe
José Antonio
JA
Páramo
Juana
J
Merino
Iván
I
Peñuelas
José Manuel García
JM
Verdugo
Beatriz
B
Pelacho
Felipe
F
Prosper
D017667:Adipocytes / Q000166:cytology*; D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D006352:Heart Ventricles / Q000503:physiopathology; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009204:Myocardial Revascularization; D019899:Paracrine Communication; D010641:Phenotype; D049268:Positron-Emission Tomography; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism; D020257:Ventricular Remodeling; D000097792:Tissue Inhibitor of Metalloproteinase-4
D042501:Angiogenic Proteins; D016207:Cytokines; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4