Facultad de Ciencias
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4 results
Results
- 18F-FDG metabolism in a rat model of chronic infarction: a 17-sector semiquantitative analysis(SCHATTAUER, 2007) Marti-Climent, J.M. (Josep María); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Gavira, J.J. (Juan José); Richter, J.A. (José Ángel); Barba, J. (Joaquín); Garcia-Velloso, M. J. (María José); Ecay, M. (Margarita); Mazo, M. (Manuel); Garcia-Rodriguez, A. (Alba); Garcia-de-Jalon, J.A. (José A.); Prosper-Cardoso, F. (Felipe); Abizanda-Sarasa, G. (Gloria)Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous 18F-fluoro-2-deoxy-2-D-glucose (18F-FDG) was administered and regional 18F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in 18F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of 18F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in 18F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p <0.05) that persisted throughout the study. Semi-quantitative analysis of 18F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration.
- Transplantation of adipose derived stromal cells is associated with functional improvement in a rat model of chronic myocardial infarction(Oxford University Press, 2008-05) Joffre, C. (Carine); Cemborain, A. (A.); Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Gavira, J.J. (Juan José); Planat-Benard, V. (Valérie); Boisson, M. (M.); Laharrague, P. (Patrick); Leobon, B. (Bertrand); Casteilla, L. (L.); Barba, J. (Joaquín); Ecay, M. (Margarita); Mazo, M. (Manuel); Prosper-Cardoso, F. (Felipe); Pelacho, B. (Beatriz); Penicaud, L. (Luc); Abizanda-Sarasa, G. (Gloria)Aims: To determine the effect of transplantation of undifferentiated and cardiac pre-differentiated adipose stem cells compared with bone marrow mononuclear cells (BM-MNC) in a chronic model of myocardial infarction. Methods: Ninety-five Sprague–Dawley rats underwent left coronary artery ligation and after 1month received by direct intramyocardial injection either adipose derived stem cells (ADSC), cardiomyogenic cells (AD-CMG) or BM-MNC from enhanced-Green Fluorescent Protein (eGFP) mice. The control group was treated with culture medium. Heart function was assessed by echocardiography and 18F-FDG microPET. Cell engraftment, differentiation, angiogenesis and fibrosis in the scar tissue were also evaluated by (immuno)histochemistry and immunofluorescence. Results: One month after cell transplantation, ADSC induced a significant improvement in heart function (LVEF 46.3±9.6% versus 27.7±8% pre-transplant) and tissue viability (64.78±7.2% versus 55.89±6.3% pre-transplant). An increase in the degree of angiogenesis and a decrease in fibrosis were also detected. Although transplantation of AD-CMG or BM-MNC also had a positive, albeit smaller, effect on angiogenesis and fibrosis in the infarcted hearts, this benefit did not translate into a significant improvement in heart function or tissue viability. Conclusion: These results indicate that transplantation of adipose derived cells in chronic infarct provides a superior benefit to cardiac pre-differentiated ADSC and BM-MNC.
- Transplantation of mesenchymal stem cells exerts a greater long-term effect than bone marrow mononuclear cells in a chronic myocardial infarction model in rat(Cognizant Communication Corporation, 2009-11) Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Aranda, P. (P.); Gavira, J.J. (Juan José); Soriano, M. (Mario); Alegria, E. (Eduardo); Ecay, M. (Margarita); Mazo, M. (Manuel); Garcia-Verdugo, J.M. (José Manuel); Prosper-Cardoso, F. (Felipe); Merino, J. (Juana); Pelacho, B. (Beatriz); Abizanda-Sarasa, G. (Gloria); Moreno, C. (Cristina)The aim of this study is to assess the long-term effect of mesenchymal stem cells (MSC) transplantation in a rat model of chronic myocardial infarction (MI) in comparison with the effect of bone marrow mononuclear cells (BM-MNC) transplant. Five weeks after induction of MI, rats were allocated to receive intramyocardial injection of 106 GFP-expressing cells (BM-MNC or MSC) or medium as control. Heart function (echocardiography and 18F-FDG-microPET) and histological studies were performed 3 months after transplantation and cell fate was analyzed along the experiment (1 and 2 weeks and 1 and 3 months). The main findings of this study were that both BM-derived populations, BM-MNC and MSC, induced a long-lasting (3 months) improvement in LVEF (BM-MNC: 26.61 ± 2.01% to 46.61 ± 3.7%, p < 0.05; MSC: 27.5 ± 1.28% to 38.8 ± 3.2%, p < 0.05) but remarkably, only MSC improved tissue metabolism quantified by 18FFDG uptake (71.15 ± 1.27 to 76.31 ± 1.11, p < 0.01), which was thereby associated with a smaller infarct size and scar collagen content and also with a higher revascularization degree. Altogether, results show that MSC provides a long-term superior benefit than whole BM-MNC transplantation in a rat model of chronic MI.
- MAPC transplantation confers a more durable benefit than AC133+ cell transplantation(Cognizant Communication Corporation, 2010-08-17) Collantes, M. (María); Peñuelas-Sanchez, I. (Ivan); Uriz, M. (Maialen); Araña, M. (Miriam); Coppiello, G. (Giulia); Andreu, E.J. (Enrique José); Perez-Ilzarbe, M. (Maitane); Luttun, A. (Aernout); Ecay, M. (Margarita); Prieto, J. (Jesús); Beerens, M. (Manu); Prosper-Cardoso, F. (Felipe); Pelacho, B. (Beatriz); Abizanda-Sarasa, G. (Gloria); Aranguren, X.L. (Xabier L.)There is a need for comparative studies to determine which cell types are better candidates to remedy ischemia. Here, we compared human AC133+ cells and Multipotent Adult Progenitor Cells (hMAPC) in a mouse model reminiscent of critical limb ischemia. hMAPC or hAC133+ cell transplantation induced a significant improvement in tissue perfusion (measured by microPET) 15 days post-transplantation compared to controls. This improvement persisted for 30 days in hMAPC-treated but not in hAC133+-injected animals. While transplantation of hAC133+ cells promoted capillary growth, hMAPC transplantation also induced collateral expansion, decreased muscle necrosis/fibrosis and improved muscle regeneration. Incorporation of differentiated hAC133+ or hMAPC progeny into new vessels was limited, however, a paracrine angio/arteriogenic effect was demonstrated in animals treated with hMAPC. Accordingly, hMAPC-, but not hAC133+-conditioned media, stimulated vascular cell proliferation and prevented myoblast, endothelial and smooth muscle cell apoptosis in vitro. Our study suggests that although hAC133+ cell and hMAPC transplantation bothcontribute to vascular regeneration in ischemic limbs, hMAPC exert a more robust effect through trophic mechanisms, which translated into collateral and muscle fiber regeneration. This, in turn, conferred tissue protection and regeneration with longer-term functional improvement.