Transplantation of vascular progenitor cells derived from human ES cells in a mouse model of chronic cerebral hypoperfusion

• Project/Area Number: 20590996
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Mie University
• Principal Investigator: TOMIMOTO Hidekazu Mie University, 大学院・医学系研究科, 教授 (80324648)
• Research Collaborator: WASHIDA Kazuo 京都大学, 大学院・医学研究科神経内科, 大学院生
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2008: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 慢性脳虚血 / 血管前駆細胞 / 胚性幹細胞 / 人工多能性幹細胞 / 血管新生 / iPS細胞 / 再生医療 / 大脳皮質 / 線条体 / VEGF / ES細胞 / 慢性脳低灌流 / マウス / 血管内皮

Research Abstract

Vascular progenitor cells (VPC)derived from human iPS cells were transplanted into thestriatum or cerebral cortex in a mouse model of chronic cerebral hypoperfusion, or sham-operation. Vessel-like structure were found exclusively in the striatum of the mice subjected to chronic cerebral hypoperfusion. In the striatum under chronic cerebral ischemia, there may be some factors to facilitate survival of VPC.

Research Products

• [Journal Article] Angiogenic and vasoprotective effects of adrenomedullin on prevention of cognitive decline after chronic cerebral hypoperfusion in mice. (2011)
  • Author(s): Maki T, Ihara M, Fujita Y, Nambu T, Miyashita K, Yamada M, Washida K, Nishio K, Ito H, Harada H, Yokoi H, Arai H, Itch H, Nakao K, Takahashi R, Tomimoto H
  • Journal Title: Stroke 42 Pages: 1122-1128
  • Peer Reviewed
• [Journal Article] Nonhypotensive dose of telmisartan attenuates cognitive impairment partially due to peroxisome proliferator-activated receptor-γ activation in mice with chronic cerebral hypoperfusion. (2010)
  • Author(s): Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
  • Journal Title: Stroke 41 Pages: 1798-1806
  • Peer Reviewed
• [Journal Article] A mouse model characterizing features of vascular dementia with hippocampal atrophy. (2010)
  • Author(s): Nishio K, Thara M, Yamasaki N, Kalaria RN, Makia T, Fujita Y, Ito H, Oishi N, Fukuyama H, Miyakawa T, Takahashi R, Tomimoto H
  • Journal Title: Stroke 41(6) Pages: 1278-1284
  • Peer Reviewed
• [Journal Article] Nonhypotensive dose of telmisartan attenuates cognitive impairment partially due to peroxisome proliferator-activated receptor-γ activation in mice with chronic cerebral hypoperfusion. (2010)
  • Author(s): Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R.
  • Journal Title: Stroke Volume: 41 Pages: 1798-1806
  • Peer Reviewed
• [Journal Article] A mouse model characterizing features of vascular dementia with hippocampal atrophy. (2010)
  • Author(s): Nishio K, Ihara M, Yamasaki N, Kalaria RN, Maki T, Fujita Y, Ito H, Oishi N, Fukuyama H, Miyakawa T, Takahashi R, Tomimoto H.
  • Journal Title: Stroke Volume: 41 Pages: 1278-1284
  • Peer Reviewed
• [Journal Article] Chronic cerebral hypoperfusion accelerates amyloid deposition in APPSwInd transgenic mice. (2009)
  • Author(s): Kitaguchi H, Tomimoto H, Ihara M, Shibata M, Uemura K, Kalaria RN, Kihara T, Asada-UtsugiM, Kinoshita A, Takahashi R.
  • Journal Title: Brain Research 1294 Pages: 202-210
  • Peer Reviewed
• [Journal Article] Cortical microinfarcts in Alzheimer's disease and subcortical vascular dementia (2009)
  • Author(s): Okamoto Y, Ihara M, Fujita Y, Ito H, Takahashi R, Tomimoto H.
  • Journal Title: Neuroreport 20 Pages: 990-996
  • Peer Reviewed
• [Journal Article] Edaravone, a free radical scavenger, mitigates both gray and white matter damages after global cerebral ischemia in rats (2009)
  • Author(s): Kubo K, Nakao S, Jomura S, Sakamoto S, Miyamoto E, Xu Y, Tomimoto H, Inada T, Shingu K.
  • Journal Title: Brain Research 1279 Pages: 139-146
  • Peer Reviewed
• [Journal Article] Chronic cerebral hypoperfusion accelerates amyloid deposition in APPSwInd transgenic mice (2009)
  • Author(s): Kitaguchi H, Tomimoto H, Ihara M, Shibata M, Uemura K, Kalaria RN, Kihara T, Asada-Utsugi M, Kinoshita A, Takahashi R.
  • Journal Title: Brain Research 1294 Pages: 202-210
  • Peer Reviewed
• [Journal Article] 脳血管性認知症の分子病態 (2008)
  • Author(s): 鷲田和夫、猪原匡史、冨本秀和
  • Journal Title: Medical Science Digest 34 Pages: 391-394
• [Journal Article] Cilostazol alleviates cerebral small-vessel pathology and white-matt er lesions in stroke-prone spontaneously hypertensive rats. (2008)
  • Author(s): Fujita Y, Lin JX, Takahashi R, Tomimoto H
  • Journal Title: Brain Res. 1203 Pages: 170-6
  • Peer Reviewed
• [Journal Article] Angiogenic and vasoprotective effects of adrenomedullin on prevention of cognitive decline after chronic cerebral hypoperfusion in mice.
  • Author(s): Maki T, Ihara M, Fujita Y, Nambu T, Miyashita K, Yamada M, Washida K, Nishio K, Ito H, Harada H, Yokoi H, Arai H, Itoh H, Nakao K, Takahashi R, Tomimoto H.
  • Journal Title: Stroke Volume: (印刷中)
  • Peer Reviewed
• [Presentation] マウス慢性脳低灌流モデルの認知機能障害および白質障害に対するテルミサルタンの効果 (2010)
  • Author(s): 鷲田和夫, 猪原匡史, 西尾佳子, 藤田裕之, 眞木崇州, 山田真人, 高橋淳, 呉暁峰, 木原武士, 伊東秀文, 冨本秀和, 高橋良輔
  • Organizer: 日本循環代謝学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 2010-11-17
• [Presentation] マウス慢性脳低灌流モデルに対する血管前駆細胞移植の効果 (2009)
  • Author(s): 鷲田和夫, 猪原匡史, 高橋淳, 山下潤, 伊東秀文, 冨本秀和, 高橋良輔
  • Organizer: 日本神経学会総会
  • Place of Presentation: 仙台市
  • Year and Date: 2009-05-20
• [Presentation] マウス慢性脳低灌流モデルに対する血管前駆細胞移植の効果 (2009)
  • Author(s): 鷲田和夫, 猪原匡史, 高橋淳, 山下潤, 伊東秀文, 冨本秀和, 高橋良輔
  • Organizer: 日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-20
• [Presentation] Long standing chronic cerebral hypoperfusion accelerates Aβ aggregation, brain atrophy and memory impairment PCS-2 (2009)
  • Author(s): H Tomimoto
  • Organizer: The 4th Congress of the International Society for Vascular Behavioural and Cognitive Disorders (VAS-COG)
  • Place of Presentation: Singapore
  • Year and Date: 2009-01-13
• [Presentation] Protective effect of cilostazol against the no-reflow phenomenon in transient cerebral ischemia (2009)
  • Author(s): Y Hase, Y Fujita, M Ihara, H Tomimoto
  • Organizer: The 4th Congress of the International Society for Vascular Behavioural and Cognitive Disorders (VAS-COG)
  • Place of Presentation: Singapore
• [Presentation] A role of intercellular adhesion molecules in the pathogenesis of white matter lesion ; an analysis of human brains (2009)
  • Author(s): M Yamada, M Ihara, H Tomimoto
  • Organizer: The 4th Congress of the International Society for Vascular Behavioural and Cognitive Disorders (VAS-COG)
  • Place of Presentation: Singapore
• [Presentation] A comparative study on the distribution of cortical microinfarcts between the brains with Alzheimer's disease and subcortical vascular dementia (2009)
  • Author(s): Y Okamoto, M Ihara, Y Fujita, R Takahashi, H Tomimoto
  • Organizer: The 4th Congress of the International Society for Vascular Behavioural and Cognitive Disorders (VAS-COG)
  • Place of Presentation: Singapore
• [Presentation] Binswanger病の脳機能画像 (2008)
  • Author(s): 冨本秀和
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16