title: Baculovirus-transduced, VEGF-expressing adipose-derived stem cell sheet for the treatment of myocardium infarction.
abstract: Cell sheet technology has been widely employed for the treatment of myocardial infarction (MI), but cell sheet fabrication generally requires the use of thermo-responsive dishes. Here we developed a method for the preparation of adipose-derived stem cell (ASC) sheet that obviated the need of thermo-responsive dishes. This method only required the seeding of rabbit ASC onto 6-well plates at an appropriate cell density and culture in appropriate medium, and the cells were able to develop into ASC sheet in 2 days. The ASC sheet allowed for transduction with the hybrid baculovirus at efficiencies >97%, conferring robust and prolonged (>35 days) overexpression of vascular endothelial growth factor (VEGF). The ASC sheet was easily detached by brief (10 s) trypsinization and saline wash, while retaining the extracellular matrix and desired physical properties. The ASC sheet formation and VEGF expression promoted cell survival under hypoxia in vitro. Epicardial implantation of the VEGF-expressing ASC sheet to rabbit MI models reduced the infarct size and improved cardiac functions to non-diseased levels, as judged from the left ventrical ejection fraction/myocardial perfusion. The VEGF-expressing ASC sheet also effectively prevented myocardial wall thinning, suppressed myocardium fibrosis and enhanced blood vessel formation. These data implicated the potential of this method for the preparation of genetically engineered ASC sheet and future MI treatment.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, Hsinchu 300, Taiwan; Division of Cardiovascular Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei 110, Taiwan.
authors.forename: Tsung-Szu
authors.initials: TS
authors.lastname: Yeh
authors.forename: Yu-Hua Dean
authors.initials: YH
authors.lastname: Fang
authors.forename: Chia-Hsin
authors.initials: CH
authors.lastname: Lu
authors.forename: Shao-Chieh
authors.initials: SC
authors.lastname: Chiu
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Yeh
authors.forename: Tzu-Chen
authors.initials: TC
authors.lastname: Yen
authors.forename: Yelena
authors.initials: Y
authors.lastname: Parfyonova
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Hu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D016367:Baculoviridae / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D011817:Rabbits; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042461:Vascular Endothelial Growth Factor A
keywords: Adipose-derived stem cells; Baculovirus; Cell sheet; Gene therapy; Myocardial infarction; Vascular endothelial growth factor