Use of amnion-derived mesenchymal stem cells for treatment of immune dysfunction after hematopoietic stem cell transplantation

• Project/Area Number: 17K07228
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Hyogo Medical University
• Principal Investigator: Fujimori Yoshihiro 兵庫医科大学, 医学部, 教授 (20229058)
• Co-Investigator(Kenkyū-buntansha): 相馬 俊裕 兵庫医科大学, 医学部, 非常勤講師 (40273619)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 間葉系幹細胞 / 造血幹細胞移植 / 移植片対宿主病 / 移植後血栓性微小血管障害 / 乾癬 / 乾癬様皮膚炎 / 血管内皮細胞 / 免疫抑制 / エクソソーム / 血栓性微小血管障害

Outline of Final Research Achievements

Mesenchymal stem cells (MSCs) have a capacity to differentiate into mesenchymal linages and can settle immune dysfunction. We here have obtained the MSCs from amnion of the placenta and used for treatment of immune dysfunction. When amnion-derived mesenchymal stem cells were administered to a mouse model of psoriasis, secretion of IL-17 and IL-23 were decreased and histopathological changes in psoriasis were also resolved (J Dermatol 2019). Acute graft versus host disease is a major adverse event after hematopoietic stem cell transplantation. We planned to use of amnion-derived mesenchymal stem cells for treatment of acute graft versus host disease in human. We developed a protocol for clinical examination to facilitate the use of amnion-derived mesenchymal stem cells in clinical setting (BMJ Open 2019).

Academic Significance and Societal Importance of the Research Achievements

骨髄由来間葉系幹細胞は、現在移植後急性移植片対宿主病の治療に保険適応されている。本研究では、分娩時の廃棄物である胎盤から、羊膜由来間葉系幹細胞を培養し、免疫不全の疾患の治療応用を検討した。皮膚の乾癬は、免疫異常が指摘されており、羊膜由来の間葉系幹細胞投与で軽減することが判明した。また、羊膜由来間葉系幹細胞を用いた急性性移植片対宿主病治療の医師主導治験のプロトコールを立案した。これらは、羊膜由来間葉系幹細胞の臨床応用を進めるうえで非常に重要な内容であり、社会的にも意義も深い。

Research Products

• [Journal Article] Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial (2019)
  • Author(s): Yamahara K、Hamada A、Soma T、Okamoto R、Okada M、Yoshihara S、Yoshihara K、Ikegame K、Tamaki H、Kaida K、Inoue T、Ohsugi Y、Nishikawa H、Hayashi H、Ito Y、Iijima H、Ohnishi S、Hashimoto D、Isoe T、Teshima T、Ogawa H、Sato N、Fujimori Y
  • Journal Title: BMJ Open Volume: 9 Issue: 7 Pages: e026403-e026403
  • DOI: 10.1136/bmjopen-2018-026403
  • Peer Reviewed / Open Access
• [Journal Article] Human amnion-derived mesenchymal stem cells ameliorate imiquimod-induced psoriasiform dermatitis in mice. (2019)
  • Author(s): Imai Y, Yamahara K, Hamada A, Fujimori Y, Yamanishi K
  • Journal Title: J Dermatol Volume: 46 Issue: 3 Pages: 276-278
  • DOI: 10.1111/1346-8138.14768
  • Peer Reviewed
• [Presentation] Bovine platelet lysate-derived serum NeoSERA is safe, less ethical and powerful alternative to fetal bovine serum for the culture of mesenchymal stem cells. (2019)
  • Author(s): Yamahara K, Sudo T, Hamada A, Yoshihara K, Yoshihara S, Okada M, Soma T, Ohnishi S, Fujimori Y
  • Organizer: International Society for Stem Cell Research
  • Int'l Joint Research
• [Presentation] 国産成牛多血小板血漿由来血清「NeoSERA」を用いた羊膜MSC製剤化と急性GVHD・クローン病向け医師主導治験. (2018)
  • Author(s): 山原研一, 濱田彰子, 大西俊介, 高田竜二, 須藤稔太, 岡本里香,豊嶋 崇徳、磯江 敏幸、佐藤 典宏、藤盛 好啓.
  • Organizer: 第17回日本再生医療学会総会
• [Presentation] Adult bovine-derived leukocyte and platelet-rich plasma (L-PRP) is safe, less ethical, economical and powerful alternative to fetal bovine serum for the culture of mesenchymal stem cells. (2017)
  • Author(s): Yamahara K, Sudo T, Hamada A, Kuroda S, Yoshihara K, Yoshihara S, Okada M,Soma T, Onishi S, Fujimori Y.
  • Organizer: International Society of Stem Cell Research (ISSCR) 2017 Annual Meeting
  • Int'l Joint Research