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Efficacy of epicardially delivered adipose stroma cell sheets in dilated cardiomyopathy

2013; Oxford University Press; Volume: 99; Issue: 4 Linguagem: Inglês

10.1093/cvr/cvt149

1755-3245

Hadhami Hamdi, Solène Emmanuelle Boitard, Valérie Planat‐Bénard, Julia Pouly, Hany Neamatalla, Pierre Joanne, Marie-Cécile Perier, Valérie Bellamy, Louis Casteilla, Zhenlin Li, Albert Hagège, Mathias Mericskay, Philippe Menasché, Onnik Agbulut,

Electrospun Nanofibers in Biomedical Applications

Few studies have assessed the effects of cell therapy in non-ischaemic cardiomyopathies which, however, contribute to a large number of cardiac failures. Assuming that such conditions are best suited for a global delivery of cells, we assessed the effects of epicardially delivered adipose tissue-derived stroma cell (ADSC) sheets in a mouse model of dilated cardiomyopathy based on cardiac-specific and tamoxifen-inducible invalidation of serum response factor. Three weeks after tamoxifen administration, the function of the left ventricle (LV) was assessed by echocardiography. Twenty-nine mice were then allocated to control (n = 9, non-transgenic), sham (n = 10, transgenic non-treated), and treated (n = 10, transgenic) groups. In the treated group, 3 × 106 allogeneic ADSCs were cultured for 2 days onto temperature-responsive polymers and the generated sheets were then transplanted over the surface of the heart. In 10 additional mice, the sheet was made of green fluorescent protein (GFP)-labelled ADSCs to track cell fate. Function, engraftment, and fibrosis were blindly assessed after 3 weeks. In the non-treated group, fractional shortening declined compared with baseline, whereas the sheet application resulted in its stabilization. This correlated with a lesser degree of LV remodelling, as LV end-diastolic and end-systolic diameters did not differ from baseline values. Many GFP+ cells were identified in the epicardial graft and in the myocardium. Treated animals also displayed a reduced expression of the stress-induced atrial natriuretic factor and beta-myosin heavy chain genes. These protective effects were also accompanied by a reduction of myocardial fibrosis. These results strongly suggest the functional relevance of epicardially delivered cell-seeded biomaterials to non-ischaemic heart failure.