title: Therapeutic reendothelialization by induced pluripotent stem cells after vascular injury--brief report.
abstract: OBJECTIVE
  Endothelial damage is an early requisite step for atherosclerosis after vascular injury. It has been reported that vascular wall cells can develop from induced pluripotent stem (iPS) cell-derived fetal liver kinase-1-positive (Flk-1(+)) cells. Here, we investigated the efficacies of intravenously administered iPS cell-derived Flk-1(+) cells on reendothelialization and neointimal hyperplasia in a mouse model of vascular injury.
  
  
  RESULTS
  Femoral arteries of KSN nude mice were injured using a steel wire. Mouse iPS cell-derived Flk-1(+) or Flk-1(-) cells were intravenously injected into those mice at 24 hours after vascular injury. Delivery of iPS cell-derived Flk-1(+) cells significantly attenuated neointimal hyperplasia compared with controls. Evans blue staining of the injured vessel revealed that administration of iPS cell-derived Flk-1(+) significantly enhanced reendothelialization compared with the Flk-1(-) cell control group. Recruitment of PKH26-labeled iPS cell-derived Flk-1(+) cells to the site of injury was also detectable. Expression level of CXCR4 in iPS cell-derived Flk-1(+) cells was 7.5-fold higher than that of iPS cell-derived Flk-1(-) cells. Stromal cell-derived factor-1α treatment significantly enhanced adhesion and migration of iPS cell-derived Flk-1(+) cells to the endothelia, but these were not observed in Flk-1(-) cells.
  
  
  CONCLUSIONS
  Intravenously administered iPS cell-derived Flk-1(+) cells are recruited to the site of vascular injury, thereby enhancing reendothelialization followed by suppression of neointimal hyperplasia. Administration of iPS cell-derived Flk-1(+) cells is a potentially useful therapeutic means for vascular dysfunction and prevention of restenosis after angioplasty.
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Rei
authors.initials: R
authors.lastname: Shibata
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ishii
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Kanemura
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Kito
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyake
authors.forename: Kengo
authors.initials: K
authors.lastname: Maeda
authors.forename: Tohru
authors.initials: T
authors.lastname: Tanigawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D058948:Cell Tracking / Q000379:methods; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D006965:Hyperplasia; D057026:Induced Pluripotent Stem Cells / Q000378:metabolism / Q000637:transplantation*; D007275:Injections, Intravenous; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D058426:Neointima; D019718:Receptors, CXCR4 / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D057772:Vascular System Injuries / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D000097573:Red Fluorescent Protein
chemical_list: D054377:Chemokine CXCL12; D008164:Luminescent Proteins; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2; D000097573:Red Fluorescent Protein; C514936:CXCR4 protein, mouse; C515256:Cxcl12 protein, mouse
keywords: hyperplasia; induced pluripotent stem cells; vascular system injuries