Development of cell therapy using human-derived injury/ischemia-induced stem/progenitor cells

• Project/Area Number: 18K07380
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Hyogo Medical University
• Principal Investigator: Nakagomi Takayuki 兵庫医科大学, 医学部, 教授 (80434950)
• Co-Investigator(Kenkyū-buntansha): 高木 俊範 兵庫医科大学, 医学部, 講師 (00452152) ; 松山 知弘 兵庫医科大学, 医学部, 特別招聘教授 (10219529) ; 吉村 紳一 兵庫医科大学, 医学部, 教授 (40240353) ; 久保 秀司 兵庫医科大学, 医学部, 准教授 (10441320)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 脳梗塞 / 幹細胞 / 神経再生 / 細胞移植 / 移植

Outline of Final Research Achievements

Using human-derived injury/ischemia-induced stem/progenitor cells (h-iSC), which were isolated from ischemic brain tissues of stroke patients requiring decompressive craniectomy and partial lobectomy for diffuse cerebral infarction, we transplanted h-iSC into post-stroke mouse brains to investigate the efficiency by these cells. We found that some h-iSCs survived around the injected sites and that they expressed a neuronal marker Tuj1 and MAP2. In addition, mice received h-iSC improved neurological functions compared with controls. These results indicate that h-iSC can become a novel cell-based therapy for patients with stroke in the future.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、h-iSCによる細胞移植療法は、これまで有効な治療法が限られていた脳梗塞患者に対する新規治療法になり得ることが示唆された。また、本治療法の確立及び発展は、将来、脳梗塞患者をはじめとし、様々な神経疾患に対して多大なる貢献をもたらし得ることから、本研究成果は意義あるものであると考えられた。

Research Products

• [Journal Article] Neural regeneration by regionally induced stem cells within post-stroke brains: novel therapy perspectives for stroke patients (2019)
  • Author(s): Nakagomi T, Takagi T, Beppu M, Yoshimura S, Matsuyama T
  • Journal Title: World journal of stem cells Volume: 11 Issue: 8 Pages: 452-463
  • DOI: 10.4252/wjsc.v11.i8.452
  • Peer Reviewed / Open Access
• [Presentation] ヒト脳梗塞巣由来、脳傷害/虚血誘導性多能性幹細胞（iSCs）の細胞移植効果に関する基礎研究―iSCsを用いた臨床応用のための基礎研究 (2019)
  • Author(s): 中込隆之、高木俊範、土居亜紀子、別府幹也、吉村紳一、松山知弘
  • Organizer: 第62回日本脳循環代謝学会学術集会
  • Invited
• [Presentation] Brain pericytes after ischemic stroke: a possible role as multipotent stem cells to differentiate into functional neurons (2019)
  • Author(s): Takayuki Nakagomi, Akiko Nakano-Doi, Toshinori Takagi, Mikiya Beppu, Hideaki Nishie, Rika Sakuma, Yuki Maeda, Yusuke Minato, Nami Nakagomi, Tomohiro Matsuyama
  • Organizer: The 29rd International Symposium on Cerebral Blood Flow, Metabolism & Function (Brain & Brain PET 2019)
  • Int'l Joint Research
• [Presentation] Injury-induced multipotent stem cells: basic characteristics and future perspective (2019)
  • Author(s): Toshinori Takagi, Mikiya Beppu, Kotaro Tatebayashi, Yoji Kuramoto, Akiko Nakano-Doi, Rika Sakuma, Takayuki Nakagomi, Tomohiro Matsuyama, Shinichi Yoshimura
  • Organizer: The 29rd International Symposium on Cerebral Blood Flow, Metabolism & Function (Brain & Brain PET 2019)
  • Int'l Joint Research