title: Application of cell sheet technology to bone marrow stromal cell transplantation for rat brain infarct.
abstract: Bone marrow stromal cells (BMSC) transplantation enhances functional recovery after cerebral infarct, but the optimal delivery route is undetermined. This study was aimed to assess whether a novel cell-sheet technology non-invasively serves therapeutic benefits to ischemic stroke. First, the monolayered cell sheet was engineered by culturing rat BMSCs on a temperature-responsive dish. The cell sheet was analysed histologically and then transplanted onto the ipsilateral neocortex of rats subjected to permanent middle cerebral artery occlusion at 7 days after the insult. Their behaviours and histology were compared with those in the animals treated with direct injection of BMSCs or vehicle over 4 weeks post-transplantation. The cell sheet was 27.9 ± 8.0 μm thick and was composed of 9.8 ± 2.4 × 105cells. Cell sheet transplantation significantly improved motor function when compared with the vehicle-injected animals. Histological analysis revealed that the BMSCs were densely distributed to the neocortex adjacent to the cerebral infarct and expressed neuronal phenotype in the cell sheet-transplanted animals. These findings were almost equal to those for the animals treated with direct BMSC injection. The attachment of the BMSC sheet to the brain surface did not induce reactive astrocytes in the adjacent neocortex, although direct injection of BMSCs profoundly induced reactive astrocytes around the injection site. These findings suggest that the BMSCs in cell sheets preserve their biological capacity of migration and neural differentiation. Cell-sheet technology may enhance functional recovery after ischaemic stroke, using a less invasive method. Copyright © 2014 John Wiley & Sons, Ltd.
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Shichinohe
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Houkin
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.|Department of Neurosurgery, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001253:Astrocytes / Q000166:cytology; D001522:Behavior, Animal; D001854:Bone Marrow Cells / Q000166:cytology*; D020520:Brain Infarction / Q000628:therapy*; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D017690:Cell Transplantation; D002478:Cells, Cultured; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008856:Microscopy, Fluorescence; D019579:Neocortex / Q000473:pathology; D009474:Neurons / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D017154:Stromal Cells / Q000166:cytology* / Q000637:transplantation*; D023822:Tissue Engineering / Q000379:methods*
keywords: bone marrow stromal cell; cell sheet technology; cell therapy; cerebral infarct; minimally invasive; regenerative medicine; tissue-engineering; transplantation