Novel Therapeutic Strategy using Direct Reprogramming Methods for Stroke

• Project/Area Number: 15K21181
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery; General medical chemistry
• Research Institution: Okayama University
• Principal Investigator: Yamashita Toru 岡山大学, 医歯薬学総合研究科, 講師 (60644408)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 脳梗塞 / 細胞移植 / iN細胞 / iPS細胞 / ダイレクトリプログラミング / iNS細胞 / 細胞移植療法

Outline of Final Research Achievements

We investigated the therapeutic effect of iNSC transplantation, and also monitored engrafted iNSCs after transplantation of undifferentiated murine iNSCs in ischemic striatum/cortex of the mouse brain.
We found that iNSC transplantation successfully improved the survival rate of stroke model mice with significant functional recovery from the stroke. The fate of engrafted iNSCs was that the majority of iNSCs had differentiated into astroglial cells but not into neural cells in both the sham-operated brain and the poststroke brain without forming a tumor up to 8 months after tMCAO.

Research Products

• [Int'l Joint Research] Konkuk University(韓国)
• [Journal Article] Novel Therapeutic Transplantation of Induced Neural Stem Cells for Stroke. (2017)
  • Author(s): Yamashita T, Liu W, Matsumura Y, Miyagi R, Zhai Y, Kusaki M, Hishikawa N, Ohta Y, Kim SM, Kwak TH, Han DW, Abe K.
  • Journal Title: Cell Transplant. Volume: Mar 13;26(3) Issue: 3 Pages: 461-467
  • DOI: 10.3727/096368916x692988
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Recent Progress in Cell Reprogramming Technology for Cell Transplantation Therapy (2016)
  • Author(s): Yamashita T, Abe K.
  • Journal Title: Neurologia medico-chirurgica Volume: 56 Issue: 3 Pages: 97-101
  • DOI: 10.2176/nmc.ra.2015-0309
  • NAID: 130005138149
  • ISSN: 0470-8105, 1349-8029
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Recent Progress in Therapeutic Strategies for Ischemic Stroke. (2016)
  • Author(s): Yamashita T, Abe K.
  • Journal Title: Cell Transplant. Volume: 25 Issue: 5 Pages: 893-8
  • DOI: 10.3727/096368916x690548
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Protective effect of telmisartan on neurovascular unit and inflammasome in stroke-resistant spontaneously hypertensive rats. (2015)
  • Author(s): Liu W, Yamashita T, Kurata T, Kono S, Hishikawa N, Deguchi K, Zhai Y, Abe K.
  • Journal Title: Neurol Res. Volume: 37 Issue: 6 Pages: 491-501
  • DOI: 10.1179/1743132815y.0000000002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] High Incidence of Dementia Conversion than Stroke Recurrence in Poststroke Patients of Late Elder Society. (2015)
  • Author(s): Nakano Y, Deguchi K, Yamashita T, Morihara R, Matsuzono K, Kawahara Y, Sato K, Kono S, Hishikawa N, Ohta Y, Higashi Y, Takao Y, Abe K.
  • Journal Title: J Stroke Cerebrovasc Dis. Volume: 24 Issue: 7 Pages: 1621-8
  • DOI: 10.1016/j.jstrokecerebrovasdis.2015.03.037
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Telmisartan promotes potential glucose homeostasis in stroke-resistant spontaneously hypertensive rats via peroxisome proliferator-activated receptor γ activation. (2015)
  • Author(s): Omote Y, Deguchi K, Kurata T, Yamashita T, Sato K, Hishikawa N, Abe K.
  • Journal Title: Curr Neurovasc Res. Volume: 12 Pages: 91-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neurovascular protection by telmisartan via reducing neuroinflammation in stroke-resistant spontaneously hypertensive rat brain after ischemic stroke. (2015)
  • Author(s): Kono S, Kurata T, Sato K, Omote Y, Hishikawa N, Yamashita T, Deguchi K, Abe K.
  • Journal Title: J Stroke Cerebrovasc Dis. Volume: 24 Issue: 3 Pages: 537-47
  • DOI: 10.1016/j.jstrokecerebrovasdis.2014.09.037
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Novel therapeutic transplantation of induced neural stem cells for stroke (2016)
  • Author(s): Yamashita T, Shang J, Nakano Y, Morihara R, and Abe K
  • Organizer: The 9th Pan Pacific Symposium on Stem Cell and Cancer Research
  • Place of Presentation: Taichung, Taiwan
  • Year and Date: 2016-05-14
  • Int'l Joint Research
• [Presentation] Novel cell transplantation therapy for stroke using induced neural stem cells (2016)
  • Author(s): Yamashita T, Morihara R and Abe K
  • Organizer: The 9th International Symposium on Neuroprotection Neurorepair 2016
  • Place of Presentation: Leipzig, Germany
  • Year and Date: 2016-04-19
  • Int'l Joint Research
• [Presentation] ダイレクトリプログラミングによる神経再生治療の展望 (2016)
  • Author(s): 山下徹、阿部康二
  • Organizer: 日本骨髄間葉系幹細胞治療学会第1回学術集会
  • Place of Presentation: 札幌
  • Invited
• [Presentation] 神経再生最前線～リハビリでなぜ麻痺は回復するのか～ (2016)
  • Author(s): 山下徹、阿部康二
  • Organizer: 神経再生・ロボットリハビリ シンポジウム
  • Place of Presentation: 京都
  • Invited
• [Presentation] 新規神経幹細胞（iNSCs）は脳梗塞を治療しうるか？ (2015)
  • Author(s): 山下徹、阿部康二
  • Organizer: 第27回日本脳循環代謝学会総会
  • Place of Presentation: 富山
  • Year and Date: 2015-10-30
  • Invited
• [Presentation] White matter change and AD pathology in a novel mice model (2015)
  • Author(s): Yamashita T, Yun Zhai and Abe K
  • Organizer: Asia Pacific Stroke Conference 2015
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2015-10-02
  • Int'l Joint Research
• [Presentation] Strong improvement of ApoE/LDL-R signals and amyloidgenesis by telmisartan in post-stroke SHR-SR (2015)
  • Author(s): Yamashita T, Zhai Y, Kono S, Nakano Y, Morihara R, Deguchi K, and Abe K
  • Organizer: BRAIN 2015
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-06-27
  • Int'l Joint Research
• [Presentation] Direct Reprogrammed Neuronal Cells as a Novel Resource for Cell Transplantation Therapy (2015)
  • Author(s): Yamashita T and Abe K.
  • Organizer: The 8th Pan Pacific Symposium on Stem Cell and Cancer Research
  • Place of Presentation: Hsinchu, Taiwan
  • Year and Date: 2015-04-10
  • Int'l Joint Research
• [Book] Mebio ～神経疾患の再生医療～ (2016)
  • Author(s): 山下徹、阿部康二 （分担執筆）
  • Total Pages: 98
  • Publisher: メジカルビュー社
• [Book] 日本臨牀 脳梗塞に対する再生医療～ES細胞・iPS細胞・iN細胞～ (2016)
  • Author(s): 山下徹、阿部康二 （分担執筆）
  • Total Pages: 165
  • Publisher: 日本臨牀社
• [Book] Clinical Neuroscience 脳梗塞モデルにおける新規神経幹細胞（iNSCs）移植 (2016)
  • Author(s): 山下徹、阿部康二 （分担執筆）
  • Total Pages: 98
  • Publisher: 中外医学社