Novel regenerative therapies based on injury-induced neural stem cells obtained from patients with stroke

• Project/Area Number: 15K06723
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Hyogo Medical University
• Principal Investigator: Nakagomi Takayuki 兵庫医科大学, 医学部, 准教授 (80434950)
• Co-Investigator(Kenkyū-buntansha): 松山 知弘 兵庫医科大学, 医学部, 教授 (10219529) ; 田中 康恵 兵庫医科大学, 医学部, 助教 (30723499) ; 吉村 紳一 兵庫医科大学, 医学部, 教授 (40240353)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 脳梗塞 / 幹細胞 / 神経再生

Outline of Final Research Achievements

Using a mouse model of cerebral infarction, we have previously demonstrated that neural stem/progenitor cells (NSPCs) develop within ischemic areas. The injury/ischemia-induced NSPCs (iNSPCs) likely originate in part from brain pericytes and they have the potential to differentiate into neural lineages. However, it is essential to understand the traits of iNSPCs in human brain for possible applications in stem cell-based therapies for stroke patients. To examine this, putative iNSPCs were extracted from ischemic brain tissue obtained from elderly stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction. Immunohistochemistry showed that nestin+ iNSPCs were localized near blood vessels within ischemic areas. Isolated iNSPCs also expressed nestin and demonstrated high proliferative potential. Furthermore, they formed neurosphere-like cell clusters and differentiated into neuronal lineages in vitro.

Research Products

• [Journal Article] Identification of multipotent stem cells in human brain tissue following stroke (2017)
  • Author(s): Kotaro Tatebayashi, Yasue Tanaka, Akiko Nakano-Doi, Rika Sak Saeko Kamachi, Manabu Shirakawa, Kazutaka Uchida, Hiroto Kageyamauma,, Toshinori Takagi, Shinichi Yoshimura, Tomohiro Matsuyama, Takayuki Nakagomi
  • Journal Title: Stem Cells Development Volume: 未定 Issue: 11 Pages: 787-797
  • DOI: 10.1089/scd.2016.0334
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Novel Regenerative Therapies Based on Regionally Induced Multipotent Stem Cells in Post-Stroke Brains: Their Origin, Characterization, and Perspective (2017)
  • Author(s): Takagi Toshinori、Yoshimura Shinichi、Sakuma Rika、Nakano-Doi Akiko、Matsuyama Tomohiro、Nakagomi Takayuki
  • Journal Title: Translational Stroke Research Volume: 8 Issue: 6 Pages: 515-528
  • DOI: 10.1007/s12975-017-0556-0
  • Peer Reviewed
• [Presentation] ヒト脳傷害誘導性多能性幹細胞の性状とその特徴 (2018)
  • Author(s): 髙木俊範、立林洸太朗、別府幹也、蔵本要二、土居亜紀子、佐久間理香、中込隆之、松山知弘、吉村紳一
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] Ischemia-induced multipotent stem cells in human cerebral infarction (2018)
  • Author(s): Kotaro Tatebayashi, Toshinori Takagi, Akiko Nakano-Doi, Rika Sakuma, Yasue Tanaka, Saeko Kamachi, Manabu Shirakawa, Kazutaka Uchida, Hiroto Kageyama, Takayuki Nakagomi, Tomohiro Matsuyama, Shinichi Yoshimura
  • Organizer: International Stroke Conference 2018
  • Int'l Joint Research
• [Presentation] ヒト脳梗塞巣における脳傷害誘導性幹細胞の確立 (2017)
  • Author(s): 髙木俊範、立林洸太朗、別府幹也、蔵本要二、中込隆之、松山知弘、吉村紳一.
  • Organizer: 第18回日本分子脳神経外科学会
• [Presentation] ヒト脳梗塞組織における多能性幹細胞の同定 (2017)
  • Author(s): 立林洸太朗、髙木俊範、土居亜紀子、佐久間理香、田中康江、白川学、影山博人、内田和孝、蒲地紗栄子、中込隆之、松山知弘
  • Organizer: 第60回日本脳循環代謝学会
• [Book] 血行再建療法時代の脳保護療法と再生医療：虚血誘導性多能性幹細胞とその臨床応用への展開 (2018)
  • Author(s): 松山知弘、中込隆之、高木俊範、吉村紳一
  • Total Pages: 5
  • Publisher: 分子脳血管病. 先端医学社
• [Book] 神経筋細胞による研究：傷害誘導性神経・多能性幹細胞 (2018)
  • Author(s): 高木俊範、吉村紳一、中込隆之、松山知弘
  • Total Pages: 5
  • Publisher: Clinical Neuroscience. 中外医学社