title: Autologous bone-marrow mesenchymal stem cell implantation and endothelial function in a rabbit ischemic limb model.
abstract: BACKGROUND
  The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs) implantation improves endothelial dysfunction in a rabbit ischemic limb model.
  
  
  METHODS
  We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n = 20) or saline was injected as a control group (n = 20). LBF was measured using an electromagnetic flowmeter. A total of 10(6) MSCs were implanted into each ischemic limb.
  
  
  RESULTS
  Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber) was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of N(G)-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar.
  
  
  CONCLUSIONS
  These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Mikami
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.forename: Keigo
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Maruhashi
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: Masato
authors.initials: M
authors.lastname: Kajikawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ochi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishimura
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tsuji
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kato
authors.forename: Chikara
authors.initials: C
authors.lastname: Goto
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply* / Q000503:physiopathology; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D011817:Rabbits; D020127:Recovery of Function / Q000502:physiology*; D014182:Transplantation, Autologous; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D019335:Nitroarginine; D000109:Acetylcholine