title: Enhanced angiogenesis by transplantation of mesenchymal stem cell sheet created by a novel magnetic tissue engineering method.
abstract: OBJECTIVE
  Therapeutic angiogenesis with cell transplantation represents a novel strategy for severe ischemic diseases. However, some patients have poor response to such conventional injection-based angiogenic cell therapy. Here, we investigated a therapeutic potential of mesenchymal stem cell (MSC) sheet created by a novel magnetite tissue engineering technology for reparative angiogenesis.
  
  
  RESULTS
  Human MSCs incubated with magnetic nanoparticle-containing liposomes were cultured, and a magnet was placed on the reverse side. Magnetized MSCs formed multilayered cell sheets according to magnetic force. Nude mice were subjected to unilateral hind limb ischemia and separated into 3 groups. For the control group, saline was injected into ischemic tissue. In the MSC-injected group, mice received magnetized MSCs by conventional needle injections without sheet formula as a control cell group. In the MSC-sheet group, MSC sheet was layered onto the ischemic tissues before skin closure. Blood flow recovery and the extent of angiogenesis were assessed by a laser Doppler blood flowmetry and histological capillary density, respectively. The MSC-sheet group had a greater angiogenesis in ischemic tissues compared to the control and MSC-injected groups. The angiogenic and tissue-preserving effects of MSC sheets were attributable to an increased expression of vascular endothelial growth factor and reduced apoptosis in ischemic tissues. In cultured MSCs, magnetic labeling itself inhibited apoptosis via a catalase-like antioxidative mechanism.
  
  
  CONCLUSIONS
  MSC sheet created by the novel magnetic nanoparticle-based tissue engineering technology would represent a new modality for therapeutic angiogenesis and tissue regeneration.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishii
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Numaguchi
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Kito
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Kazunori
authors.initials: K
authors.lastname: Shimizu
authors.forename: Akira
authors.initials: A
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Honda
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004195:Disease Models, Animal; D052203:Ferrosoferric Oxide; D006614:Hindlimb; D006801:Humans; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D017078:Laser-Doppler Flowmetry; D008081:Liposomes; D008280:Magnetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology; D018919:Neovascularization, Physiologic; D012039:Regional Blood Flow; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D008081:Liposomes; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D052203:Ferrosoferric Oxide