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Adipose Stromal Vascular Fraction improves cardiac function in chronic myocardial infarction through differentiation and paracrine activity
Authors: Manuel Mazo, Arantxa Cemborain, Juan José Gavira, Gloria Abizanda, Miriam Araña, Mayte Casado, Mario Soriano, Salomón Hernández, Cristina Moreno, Margarita Ecay, Edurne Albiasu, Miriam Belzunce, Josune Orbe, José Antonio Páramo Juana Merino, Iván Peñuelas, José Manuel García Verdugo, Beatriz Pelacho, Felipe Prosper
Source: Cell Transplantation
Publisher: Cognizant Communication Corporation
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Abstract:
AIMS: 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.METHODS AND RESULTS: MI was induced in 82 rats by permanent coronary artery ligation and 5 weeks later, rats were allocated to receive an intra-myocardial injection of 10⁷ GFP-expressing fresh SVF-cells or culture media as control. Heart function and 8 tissue metabolism were determined by echocardiography and 18F-FDG-microPET, respectively, and histological studies were performed for up to 3 months after 10 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 pro-inflammatory (MCP-1) cytokines, as well as TIMP1 and TIMP4, was demonstrated in vitro and in vivo, strongly suggesting that they have a trophic effect.CONCLUSIONS: 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.Document Type:
DOI: http://dx.doi.org/10.3727/096368911X623862
Appeared or available online: February 2, 2012
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