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Isolation, Culture, and Adipogenic Induction of Stromal Vascular Fraction-derived Preadipocytes from Mouse Periaortic Adipose Tissue
Published on: July 21, 2023
Adipose stromal vascular fraction improves cardiac function in chronic myocardial infarction through differentiation
Manuel Mazo1, Arantxa Cemborain, Juan José Gavira
1Hematology and Cell Therapy and Foundation for Applied Medical Research, Division of Cancer, Clínica Universitaria, University of Navarra, Navarra, Spain.
Insights
Adipose-derived stromal vascular fraction (SVF) cells significantly improve heart function and tissue metabolism for 3 months in a chronic myocardial infarction (MI) rat model. These cells promote cardiac regeneration and long-term benefits through direct and indirect mechanisms.
Area of Science:
- Regenerative Medicine
- Cardiovascular Research
- Cell Therapy
Background:
- Acute myocardial infarction (MI) treatment with adipose-derived cells is established, but chronic effects remain unclear.
- Investigating long-term efficacy of stromal vascular fraction (SVF) cell transplantation in chronic MI is crucial.
Purpose of the Study:
- To evaluate the long-term impact of SVF cell transplantation on cardiac function and metabolism in a rat model of chronic MI.
- To elucidate the mechanisms underlying SVF cell-mediated cardiac repair.
Main Methods:
- Chronic MI induced in 82 rats via coronary artery ligation.
- Intramyocardial injection of 10^7 GFP-expressing SVF cells or control media 5 weeks post-MI.
- Assessment of cardiac function (echocardiography), metabolism (18F-FDG-microPET), and histology up to 3 months post-transplantation.
Main Results:
- SVF cell transplantation led to significant, long-lasting (3 months) improvements in cardiac function and metabolism.
- Histological analysis revealed increased revascularization, positive cardiac remodeling, smaller infarct size, thicker infarct wall, reduced fibrosis, and lower hypertrophy.
- Engrafted SVF cells were detected for at least 3 months, contributing to vasculature and myofibroblasts, and releasing angiogenic and trophic factors.
Conclusions:
- SVF cell transplantation offers significant long-term functional benefits in chronic MI.
- SVF cells promote cardiac tissue regeneration via direct cellular contributions and indirect paracrine effects.
- SVF cell therapy holds potential for treating chronic ischemic heart disease.
Abstract:
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.
