Endogenous repair mechanisms after human stem cell transplantation following stroke

• Project/Area Number: 25861282
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Nagasaki University
• Principal Investigator: HIU Takeshi 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (00404260)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 神経幹細胞 / 脳梗塞 / シナプス / 再生医療 / ヒト神経幹細胞

Outline of Final Research Achievements

Vehicle or human neural progenitor cells (hNPCs) derived from fetal cortex were transplanted into the ischemic cortex of Nude rats at 7 days after distal middle cerebral artery occlusion. Transplantation of hNPCs significantly improved behavioral recovery after stroke compared to vehicle-treated rats at 4 weeks post-transplantation.hNPC-treated rats had a higher density of glutamatergic synapses in layer 5 at 4 weeks post-transplantation, compared to vehicle-treated rats.
These results provide novel new information about the organization of synaptic circuitry and its plasticity after stem cell therapy. These data suggest that stem cells alter the synaptic remodeling of glutamatergic synapses after stroke and this is coincident with stem cell-induced functional recovery.

Research Products

• [Journal Article] Stem cell transplantation enhances endogenous brain repair after experimental stroke (2015)
  • Author(s): Horie N, Hiu T, Nagata I
  • Journal Title: Neurol Med Chir (Tokyo) Volume: 55(2) Pages: 107-112
  • NAID: 130004922276
  • Peer Reviewed
• [Journal Article] Microsurgical Clipping for Recurrent Aneurysms after Initial Endovascular Coil Embolization (2015)
  • Author(s): Izumo T, Matsuo T, Morofuji Y, Hiu T, Horie N, Hayashi K, Nagata I
  • Journal Title: World Neurosurg Volume: 83(2) Pages: 211-218
  • Peer Reviewed
• [Journal Article] Intra-arterial transplantation of low-dose stem cells provides functional recovery without adverse effects after stroke. (2015)
  • Author(s): Fukuda Y, Horie N, Satoh K, Yamaguchi S, Morofuji Y, Hiu T, Izumo T, Hayashi K, Nishida N, Nagata I
  • Journal Title: Cell Mol Neurobiol Volume: 35 (3) Pages: 399-406
  • Peer Reviewed
• [Journal Article] Candesartan improves ischemia-induced impairment of the blood-brain barrier in vitro (2015)
  • Author(s): So G, Nakagawa S, Morofuji Y, Hiu T, Hayashi K, Tanaka K, Suyama K, Deli MA, Nagata I, Matsuo T, Niwa M
  • Journal Title: Cell Mol Neurobiol Volume: 35(4) Pages: 563-572
  • Peer Reviewed
• [Journal Article] 脳梗塞に対するヒト神経幹細胞移植後の内在性修復メカニズム -幹細胞は興奮性シナプスを増加させる- (2015)
  • Author(s): 日宇 健, 堀江信貴, Tonya Bliss, 山口 将, 福田 雄高, 堤 圭介, 松尾 孝之,永田 泉, Gary Steinberg
  • Journal Title: 脳循環代謝 Volume: -
  • NAID: 130005093687
• [Journal Article] Carotid artery stenting with proximal and distal protection for radiation-induced carotid stenosis: a case report (2014)
  • Author(s): Fukuda S, Hayashi K, Horie N, Morikawa M, Yamaguchi S, Morofuji Y, Hiu T, Nagata I
  • Journal Title: No Shinkei Geka Volume: 42(7) Pages: 635-39
  • Peer Reviewed
• [Journal Article] De Novo Ivy Sign Indicates Postoperative Hyperperfusion in Moyamoya Disease (2014)
  • Author(s): Horie N, Morikawa M, Morofuji Y, Hiu T, Izumo T, Hayashi K, Nagata I
  • Journal Title: Stroke Volume: 45 (5) Pages: 1488-1491
  • Peer Reviewed
• [Presentation] 近年における破裂前交通脳動脈瘤治療法選択の動向 ― 長崎SAH研究会data baseにおける過去10年間の後方視的検討 ― (2015)
  • Author(s): 日宇 健, 堤 圭介, 福田 雄高, 出雲 剛, 林 健太郎, 北川 直毅、笠 伸年, 上之郷眞木雄, 小野 智憲, 戸田 啓介, 馬場 啓至, 松尾 孝之, 永田 泉
  • Organizer: Stroke 2015
  • Place of Presentation: リーガロイヤル広島（広島県）
  • Year and Date: 2015-03-26 – 2015-03-29
• [Presentation] 近年における破裂前交通脳動脈瘤治療法選択の動向 ― 長崎SAH研究会data baseにおける過去10年間764例の後方視的検討 ― (2014)
  • Author(s): 日宇 健, 堤 圭介, 福田 雄高, 出雲 剛, 林 健太郎, 北川 直毅、笠 伸年, 上之郷眞木雄, 小野 智憲, 戸田 啓介, 馬場 啓至, 永田 泉
  • Organizer: 第30回日本脳神経血管内治療学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県）
  • Year and Date: 2014-12-04 – 2014-12-06
• [Presentation] 脳梗塞に対するヒト神経幹細胞移植後の内在性修復メカニズム (2014)
  • Author(s): 日宇 健, 堀江 信貴, Tonya Bliss, 山口 将、福田 雄高、松尾 孝之、永田 泉、Gary Steinberg
  • Organizer: 第26回日本脳循環代謝学会総会
  • Place of Presentation: 岡山コンベンションセンター（岡山市）
  • Year and Date: 2014-11-21 – 2014-11-22
  • Invited
• [Presentation] Current management of incidental small (<5 mm) unruptured intracranial aneurysms (2014)
  • Author(s): Takeshi Hiu, Keisuke Tsutsumi, Masahiro Yonekura, Yuutaka Fukuda, Tsuyoshi Izumo, Kentaro Hayashi, Makio Kaminogo, Hiroshi Baba and Izumi Nagata
  • Organizer: 13th Kyushu-Ho Youngnam Neurosurgical Joint Meeting, Daegu (Korea), Luncheon Symposium
  • Place of Presentation: Daegu, Korea
  • Year and Date: 2014-11-08
  • Invited
• [Presentation] 脳梗塞に対するヒト神経幹細胞移植後の内在性修復メカニズム (2014)
  • Author(s): 日宇 健, 堀江 信貴, Tonya Bliss, Gary Steinberg, 永田 泉
  • Organizer: 日本脳神経外科学会 第73回学術総会
  • Place of Presentation: グランドプリンスホテル新高輪（東京都港区）
  • Year and Date: 2014-10-09 – 2014-10-11
• [Presentation] Post-ischemic synaptic remodeling is enhanced by transplanted human neural stem cells (2013)
  • Author(s): Hiu Takeshi
  • Organizer: World Congress of Neurosurgery
  • Place of Presentation: Seoul (Korea)
• [Presentation] 脳梗塞に対する神経幹細胞移植後の機能回復の内在性メカニズム：シナプスの可塑性との関連性 (2013)
  • Author(s): 日宇 健
  • Organizer: 第25回日本脳循環代謝学会総会
  • Place of Presentation: 京王プラザホテル（札幌市）
• [Presentation] Synaptic Remodeling in the Ischemic Brain is Enhanced by Stem Cell Treatment (2013)
  • Author(s): Hiu Takeshi
  • Organizer: Congress of Neurological Surgeons
  • Place of Presentation: San Francisco (USA)
• [Presentation] Potentiation of GABA-mediated synaptic inhibition as a novel target for post-stroke recovery (2013)
  • Author(s): Hiu Takeshi
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego (USA)
• [Presentation] Post-ischemic synaptic remodeling is modulated by transplanted human neural stem cells (2013)
  • Author(s): Hiu Takeshi
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego (USA)