Abstract 11267: Efficacy of Epicardially Delivered Adipose Stromal Cell Sheets in Dilated Cardiomyopathy
Introduction. Few studies have assessed the effects of cell therapy in nonischemic 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.
Methods. Three weeks after tamoxifen administration, the function of the left ventricle (LV) was assessed by echocardiography. Twenty-nine mice were then randomly allocated to control (n=9, non-transgenic), sham (n=10, transgenic untreated) and treated (n=10) groups. In the treated group, 3×106 allogeneic ADSCs were cultured for 2 days onto temperature-sensitive polymers and the generated sheets were then grafted over the surface of the LV. In 10 additional mice, the sheet was made of GFP-labeled ADSCs to track cell fate. Function, engraftment, and fibrosis were blindly assessed after 3 weeks; PCR were also performed to screen a wide array of cardiac genes. All animals were ciclosporine-immunosuppressed. Data are expressed as means with 95% CI.
Results. In the untreated group, shortening fraction declined compared with baseline (17% [14 ; 20] vs 26% [21; 30], p=0.0005), whereas the sheet application resulted in its stabilization (22% [19 ; 25] vs 22% [19 ; 25], p=0.87). This correlated with a lesser degree of LV remodeling as LV end-diastolic diameter did not differ from baseline values (4.1 mm [3.8 ; 4.4] vs 3.9 mm [3.7 ; 4.2], p=0.33) whereas it significantly increased in the untreated group (4.4 mm [4.0 ; 4.9] vs 3.9 mm [3.5 ; 4.2], p=0.04). Changes in LV end-systolic diameter featured similar patterns. Many GFP+ cells were identified in the epicardial construct and in the myocardium. Treated animals also displayed a reduced expression of the stress-induced ANF (p=0.009) and ß-myosin heavy chain genes (p=0.005). These protective effects were also accompanied by a reduction of myocardial fibrosis (21% [19 ; 23] vs 15% [13 ; 17], p=0.002).
Conclusions. These results strongly suggest the functional relevance of epicardially-delivered cell-seeded biomaterials to nonischemic heart failure.
- © 2012 by American Heart Association, Inc.