Journal
CELL TRANSPLANTATION
Volume 21, Issue 12, Pages 2723-2733Publisher
COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096368912X638847
Keywords
Adipose-derived stem cells (ADSCs); Cardiac ischemia/reperfusion; Angiogenesis; Heart remodeling
Funding
- Ministerio de Ciencia e Innovacion: ISCIII [PI070474, CP09/00333]
- Ministerio de Ciencia e Innovacion: RETIC [RD06/0014, PLE2009-0116]
- FEDER fund from Comunidad de Trabajo de los Pirineos (CTP)
- FEDER fund from European Union Framework Project VII (INELPY)
- FEDER fund from Caja de Ahorros de Navarra (Programa Tu Eliges: Tu Decides)
- UTE project CIMA
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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.
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