虚血性難聴に対する骨髄幹細胞を用いた再生治療の試み

2007 Fiscal Year Annual Research Report

• Project/Area Number: 19659437
• Research Institution: Ehime University
• Principal Investigator: 安藤 志保 Ehime University, 医学部附属病院, 医員 (90448374)
• Co-Investigator(Kenkyū-buntansha): 暁 清文 愛媛大学, 大学院・医学系研究科, 教授 (00108383) ; 秦 龍二 愛媛大学, 大学院・医学系研究科, 准教授 (90258153) ; 出崎 順三 愛媛大学, 大学院・医学系研究科, 講師 (00036451) ; 朱 鵬翔 愛媛大学, 大学院・医学系研究科, 助教 (40380216)
• Keywords: Cochlear ischemia / Hematopoietic stem cell / Apoptosis / Regeneration

Research Abstract

骨髄造血幹細胞を用いて、砂ネズミ虚血性難聴モデルで再生治療を行った。その結果骨髄造血幹細胞を内耳に移植すると、聴性脳幹反応(ABR)の虚血性障害が有意に改善した。更に蝸牛を摘出し、有毛細胞の細胞死の有無を検討すると、幹細胞治療群で有意に内有毛細胞の虚血性細胞死が抑制されていた。次いで細胞死抑制機構における骨髄造血幹細胞の役割を検討するために、骨髄造血幹細胞を蛍光色素でラベリングし経時的に細胞動態を調べると、内耳に移植された骨髄造血幹細胞は鼓室階に留まっており、内有毛細胞に再分化したり、障害した内有毛細胞と融合した骨髄造血幹細胞は見いだせなかった。一方骨髄造血幹細胞から何らかの栄養因子が分泌され虚血性内有毛細胞死を防御する可能性が考えられたので、文献的に報告のあった、glialcell line-derived neurotrophic factor (GDNF)、brain derived neurotrophic factor(BDNF)、fibroblast growth factor(FGF)1、FGF2、angiopoietin-1(Ang1)、neurotrophin-3 (NT3) anderythropoietin (EPO)に関して検討した。その結果幹細胞治療群の蝸牛では有意にGDNFのタンパク量が増大していることが明らかとなった。以上のことより、骨髄造血幹細胞は直接内有毛細胞に再分化したり障害内有毛細胞と融合するのではなく、内耳でのGDNFの発現を増大させることで虚血性内耳障害を軽減させることが明らかとなった。

Research Products

• [Journal Article] Intravenous Infusion of Dihydroginsenoside Rb1 Prevents Compressive Spinal Cord Injury and Ischemic Brain Damage through Upregulation of VEGF and Bcl-xL (2007)
  • Author(s): Sakanaka M, Zhu P, Zhang Bo, Wen TC, Cao F, Ma YJ, Samukawa K, Mitsuda N, Tanaka J, Kuramoto M, Uno H, Hata R.
  • Journal Title: Journal of Neurotrauma 24 Pages: 1037-1054
  • Peer Reviewed
• [Journal Article] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects (2007)
  • Author(s): Yoshida T, Hakuba N, Morizane I, Fujita K, Cao F, Zhu P, Uchida N, Kameda K, SakanakaM, Gyo, K, Hata R
  • Journal Title: Neuroscience 145 Pages: 923-930
  • Peer Reviewed
• [Journal Article] Ginsenoside Rb 1 protects against damage to the spiral ganglion cells after cochlear ischemia (2007)
  • Author(s): Fujita K, Hakuba N, Hata R, Morizane I, Yoshida T, Shudou M, Sakanaka M, and Gyo K
  • Journal Title: Neurosci Lett 415 Pages: 113-117
  • Peer Reviewed
• [Presentation] α-synuclein promotes neuronal cell death through the activation of microglia (2007)
  • Author(s): Hata R, Zhu P, Cao F, Sakanaka M, Tanabe H.
  • Organizer: International Psychogeriatric Association 25th Anniversary Meeting
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20071014-18
• [Presentation] Risk of conversion from mild memory impairment to Altzhemier'disease in a Japanese community(from the Nakayama Study) (2007)
  • Author(s): Matsumoto N, Hata R, IshikawaT, Fukuhara R, Hokoishi K, Ikeda M, Tanabe H.
  • Organizer: International Psychogeriatric Association 25th Anniversary Meeting
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20071014-18
• [Presentation] Hematopoietic stem cells prevent hair cell death after transient cochlear ischemia through paracrine effects (2007)
  • Author(s): Yoshida T, Hata R, Hakuba N, Cao F, Zhu P, Sakanaka M, Gyo K.
  • Organizer: The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Fungtion
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20070520-24
• [Presentation] Protective effects of dihydrogeninsenoside Rb1 on ischemic brain damage and compressive spinal cord injury through upregulation of VEGF and Bcl-XL (2007)
  • Author(s): Hata R, Cao F, Zhu P, Samukawa K, Sakanaka M.
  • Organizer: The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20070520-24
• [Presentation] Overexpression of Stat3 promotes neuronal cell death through activation of microglia (2007)
  • Author(s): Hata R, Cao F, Zhu P, Sakanaka M.
  • Organizer: The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20070520-24
• [Presentation] Microglia promotes astrogliogenesis of the neural stem cells through activating Jak/Stat signahng (2007)
  • Author(s): Zhu P, Hata R, Cao F, Sakanaka M.
  • Organizer: The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20070520-24
• [Presentation] Upregulation of syntaxin1 in the ischemic cortex following permanent focal ischemia in rats (2007)
  • Author(s): Cao F, Hata R, Zhu P, Sakanaka M.
  • Organizer: The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20070520-24
• [Presentation] Targeted disruption of organic cation transporter 3 in mice reducesischemic brain injury through down-regulation of IL-6 and MCP-1 (2007)
  • Author(s): Zhu P, Hata R, Ogasawara M, Cao F, Maeyama K, Sakanaka M.
  • Organizer: The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20070520-24
• [Presentation] Delayed neuronal cell death in the brain stem after transient ischemia in gerbils (2007)
  • Author(s): Cao F, Hata R, Zhu P, Sakanaka M.
  • Organizer: The 23rd International Symposium on Cerebral Blood Flow, Metabolism & Function
  • Place of Presentation: Osaka,Japan
  • Year and Date: 20070520-24