title: Hypoxic preconditioning enhances angiogenic potential of bone marrow cells with aging-related functional impairment.
abstract: BACKGROUND
  Hypoxic preconditioning of bone marrow cells (BMCs) from young healthy individuals can enhance the cells' therapeutic potential. Considering that the response to hypoxia may differ according to the quality of the cells, we assessed the effect of hypoxic preconditioning on BMCs from aged mice and compared the difference in response between BMCs from aged and young mice.
  
  
  RESULTS
  BMCs from young (3 months) and aged (20-22 months) mice were subjected to hypoxic preconditioning by culture for 24 h in 2% O₂. Compared with BMCs from young mice, those from aged mice showed significantly fewer CD34- or c-kit-positive stem cells, higher expression of p53, and lower telomerase activity. Adhesion, survival and angiogenic potency were also lower in BMCs from aged mice, indicating an aging-related impairment. Hypoxia-preconditioned BMCs from aged mice showed enhanced adhesion, survival, and angiogenic potency with the in vitro assessments, as well as the in vivo implantation into ischemic hindlimbs. All the enhancements by hypoxic preconditioning were comparable between BMCs from aged and young mice, although the angiogenic potential of BMCs with and without hypoxic preconditioning was lower in old mice compared with young mice.
  
  
  CONCLUSIONS
  Similar responses to hypoxia by BMCs from both aged and young mice suggest that hypoxic preconditioning could be a useful method of enhancing the angiogenic potential of BMCs.
authors.affiliation: Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kubo
authors.forename: Tao-Sheng
authors.initials: TS
authors.lastname: Li
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurazumi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takemoto
authors.forename: Mako
authors.initials: M
authors.lastname: Ohshima
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Murata
authors.forename: Shunsaku
authors.initials: S
authors.lastname: Katsura
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Morikage
authors.forename: Akira
authors.initials: A
authors.lastname: Furutani
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Hamano
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002470:Cell Survival; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000637:transplantation; D006614:Hindlimb; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic; D018384:Oxidative Stress; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D019009:Proto-Oncogene Proteins c-kit; D019098:Telomerase