title: Efficacy of epicardially delivered adipose stroma cell sheets in dilated cardiomyopathy.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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 × 10(6) 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.
  
  
  CONCLUSIONS
  These results strongly suggest the functional relevance of epicardially delivered cell-seeded biomaterials to non-ischaemic heart failure.
authors.affiliation: Inserm U, Laboratory of Biosurgical Research, Paris, France.
authors.forename: Hadhami
authors.initials: H
authors.lastname: Hamdi
authors.forename: Solène Emmanuelle
authors.initials: SE
authors.lastname: Boitard
authors.forename: Valérie
authors.initials: V
authors.lastname: Planat-Benard
authors.forename: Julia
authors.initials: J
authors.lastname: Pouly
authors.forename: Hany
authors.initials: H
authors.lastname: Neamatalla
authors.forename: Pierre
authors.initials: P
authors.lastname: Joanne
authors.forename: Marie-Cécile
authors.initials: MC
authors.lastname: Perier
authors.forename: Valérie
authors.initials: V
authors.lastname: Bellamy
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.forename: Zhenlin
authors.initials: Z
authors.lastname: Li
authors.forename: Albert Alain
authors.initials: AA
authors.lastname: Hagège
authors.forename: Mathias
authors.initials: M
authors.lastname: Mericskay
authors.forename: Philippe
authors.initials: P
authors.lastname: Menasché
authors.forename: Onnik
authors.initials: O
authors.lastname: Agbulut
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000473:pathology / Q000628:therapy*; D005355:Fibrosis; D019394:Ki-67 Antigen / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000473:pathology; D010496:Pericardium; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D020257:Ventricular Remodeling
chemical_list: D019394:Ki-67 Antigen; C498355:Mki67 protein, mouse
keywords: Cardiomyopathy; Cell therapy; Fibrosis; Remodelling; Stem cells