In vitro analysis of the effect of HLA-matching on neural cell transplantation using iPS cell-based culture system

• Project/Area Number: 18H02912
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kyoto University
• Principal Investigator: Morizane Asuka 京都大学, iPS細胞研究所, 特定拠点講師 (10528730)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000); Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: パーキンソン病 / 再生医療 / 中枢神経 / 多能性幹細胞 / 細胞移植 / iPS細胞 / 移植 / ドパミン神経 / 中型有棘神経 / シナプス / 自家移植 / パーキンソン / 神経 / HLA / HLA多型

Outline of Final Research Achievements

Cell therapy using pluripotent stem cells for Parkinson's disease has been applied to clinics. The purpose of this study was to establish in vitro model system and to examine the detail of cell transplantation especially on the difference of autologous and allogeneic ones. The cells derived from multiple cell lines were induced to the cell type of donor dopamine neurons and recipient neurons, co-cultured as in vitro model of cell therapy and then analyzed. They were analyzed by immunostaining and qPCR. Their electrical activities were monitored over time. The characteristics of donor and recipient cell type were reproduced. No difference has been detected for synaptic connection nor maturations between the autologous and the allogeneic combinations. A longer period of culture experiment would provide more detailed information in future.

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病は難治疾患であり、病気の進行とともに内服治療での治療が難しくなる。将来、細胞移植が治療選択肢の一つとなることに期待されている。動物実験を用いた細胞移植の研究では移植片が生着し、疾患モデル動物の機能改善が報告されている。しかし、実験動物を用いた系ではドナー-ホスト間の神経シナプス結合がヒト神経-動物神経となるため、実際のヒト脳での移植を想定した詳細な検討が出来ない。ヒト－ヒト神経の結合をみるためには本研究のようにホスト側の神経もヒト幹細胞から誘導する必要がある。本研究はヒト脳への細胞移植を試験管内で再現する実験モデル系を開発したところに意義がある。

Research Products

• [Journal Article] 特集 神経再生医療とリハビリテーション パーキンソン病に対する再生医療とリハビリテーション (2021)
  • Author(s): 森実 飛鳥、高橋 淳
  • Journal Title: 総合リハビリテーション Volume: 49 Issue: 1 Pages: 23-28
  • DOI: 10.11477/mf.1552202127
  • ISSN: 0386-9822, 1882-1340
  • Year and Date: 2021-01-10
• [Journal Article] Therapeutics potentiating microglial p21-Nrf2 axis can rescue neurodegeneration caused by neuroinflammation (2020)
  • Author(s): A. Nakano-Kobayashi1,*, A. Fukumoto2, A. Morizane2, D. T. Nguyen3, T. M. Le3, K. Hashida3, T. Hosoya4, R. Takahashi5,J. Takahashi2, O. Hori3 and M. Hagiwara1
  • Journal Title: Science Advances Volume: 6 Issue: 46 Pages: 1-12
  • DOI: 10.1126/sciadv.abc1428
  • NAID: 120006898186
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pre-clinical study of induced pluripotent stem cell-derived dopaminergic progenitor cells for Parkinson’s disease (2020)
  • Author(s): Doi Daisuke、Magotani Hiroaki、Kikuchi Tetsuhiro、Ikeda Megumi、Hiramatsu Satoe、Yoshida Kenji、Amano Naoki、Nomura Masaki、Umekage Masafumi、Morizane Asuka、Takahashi Jun
  • Journal Title: Nature Communications Volume: 11 Issue: 1
  • DOI: 10.1038/s41467-020-17165-w
  • NAID: 120006870849
  • Peer Reviewed / Open Access
• [Journal Article] Exercise Promotes Neurite Extensions from Grafted Dopaminergic Neurons in the Direction of the Dorsolateral Striatum in Parkinson’s Disease Model Rats (2020)
  • Author(s): Torikoshi Sadaharu、Morizane Asuka、Shimogawa Takafumi、Samata Bumpei、Miyamoto Susumu、Takahashi Jun
  • Journal Title: Journal of Parkinson's Disease Volume: 10 Issue: 2 Pages: 511-521
  • DOI: 10.3233/jpd-191755
  • Peer Reviewed
• [Journal Article] Axonal Extensions along Corticospinal Tracts from Transplanted Human Cerebral Organoids (2020)
  • Author(s): Kitahara Takahiro、Sakaguchi Hideya、Morizane Asuka、Kikuchi Tetsuhiro、Miyamoto Susumu、Takahashi Jun
  • Journal Title: Stem Cell Reports Volume: 15 Issue: 2 Pages: 467-481
  • DOI: 10.1016/j.stemcr.2020.06.016
  • Peer Reviewed / Open Access
• [Journal Article] 特集 パーキンソン病診療最前線 パーキンソン病に対する細胞移植治療 (2019)
  • Author(s): 森実飛鳥、高橋 淳
  • Journal Title: Pharma Medica Volume: 37 Issue: 4 Pages: 53-57
  • DOI: 10.34449/J0001.37.04_0053-0057
  • ISSN: 0289-5803
  • Year and Date: 2019-04-20
• [Journal Article] 中枢神経疾患領域におけるiPS細胞を用いた細胞療法 (2019)
  • Author(s): 森実飛鳥
  • Journal Title: Bio Clinica Volume: 34 Pages: 1296-1300
• [Journal Article] MicroRNA-Based Separation of Cortico-Fugal Projection Neuron-Like Cells Derived From Embryonic Stem Cells (2019)
  • Author(s): Sunohara Tadashi、Morizane Asuka、Matsuura Satoshi、Miyamoto Susumu、Saito Hirohide、Takahashi Jun
  • Journal Title: Frontiers in Neuroscience Volume: 13 Pages: 1141-1141
  • DOI: 10.3389/fnins.2019.01141
  • Peer Reviewed / Open Access
• [Journal Article] Cell therapy for Parkinson’s disease with induced pluripotent stem cells (2019)
  • Author(s): 森実飛鳥
  • Journal Title: Rinsho Shinkeigaku Volume: 59 Issue: 3 Pages: 119-124
  • DOI: 10.5692/clinicalneurol.cn-001235
  • NAID: 130007626621
  • ISSN: 0009-918X, 1882-0654
  • Open Access
• [Journal Article] パーキンソン病に対するiPS細胞を用いた細胞移植 (2018)
  • Author(s): 森実飛鳥、高橋 淳
  • Journal Title: 日本臨床 Volume: 76 Pages: 544-549
• [Presentation] CELL THERAPY FOR PARKINSON’S DISEASE WITH INDUCED PLURIPOTENT STEM CELLS (2021)
  • Author(s): Asuka Morizane
  • Organizer: Innovations in Regenerative Medicine
  • Int'l Joint Research / Invited
• [Presentation] CELL THERAPY FOR PARKINSON’S DISEASE WITH INDUCED PLURIPOTENT STEM CELLS (2021)
  • Author(s): Asuka Morizane
  • Organizer: 15th International Conference on Alzheimer’s and Parkinson’s Diseases (ADPD2021)
  • Int'l Joint Research / Invited
• [Presentation] 脳でのiPS細胞移植治療における免疫反応検出法 (2020)
  • Author(s): 森実 飛鳥, 土井 大輔, 菊地 哲広, 高橋 淳
  • Organizer: 第19回日本再生医療学会総会
• [Presentation] DETECTION OF IMMUNE REACTION AFTER IPSC-DERIVED DOPAMINE NEURAL TRANSPLANTATION IN BRAIN (2020)
  • Author(s): Asuka Morizane, Tetsuhiro Kikuchi, Daisuke Doi, Jun Takahashi
  • Organizer: ISSCR 2020
  • Int'l Joint Research
• [Presentation] iPS細胞を用いた神経疾患の再生治療 (2020)
  • Author(s): 森実飛鳥、高橋 淳
  • Organizer: 第41回 日本炎症・再生医学会
  • Invited
• [Presentation] CONTROL OF IMMUNE RESPONSE IN THE CELL THERAPY FOR PARKINSON’S DISEASE (2019)
  • Author(s): Asuka Morizane, Tetsuhiro Kikuchi, Daisuke Doi, Jun Takahashi
  • Organizer: ISSCR2019 LA Annual Meeting
  • Int'l Joint Research
• [Presentation] Translating a stem cell-derived dopamine cell to a clinical drafting trial for PD (2019)
  • Author(s): Asuka Morizane
  • Organizer: 5th World Parkinson Congress, Kyoto
  • Int'l Joint Research / Invited
• [Presentation] 神経疾患に対するiPS細胞を用いた細胞移植治療の臨床応用 (2019)
  • Author(s): 森実飛鳥
  • Organizer: R&Dカンファレンス 九州大学脳神経外科
  • Invited
• [Presentation] Clinical application of iPS cell therapy for Parkinson’s disease (2019)
  • Author(s): Asuka Morizane
  • Organizer: Cell Therapy world asia 2019
  • Int'l Joint Research / Invited
• [Presentation] 人工多能性幹細胞(iPS細胞)由来神経前駆細胞を用いた 細胞移植治療と移植免疫 (2019)
  • Author(s): 森実 飛鳥, 土井 大輔, 菊地 哲広, 高橋 淳
  • Organizer: 第78回日本脳神経外科学会総会
• [Presentation] Clinical Application of iPS Cell Therapy For Parkinson’s Disease (2019)
  • Author(s): Asuka Morizane, Jun Takahashi
  • Organizer: Cell & Therapy world asia 2019 SelectBIO
  • Int'l Joint Research / Invited
• [Presentation] Cell therapy for Parkinson’s disease with induced pluripotent stem cells (2018)
  • Author(s): Asuka Morizane
  • Organizer: East Asia Neurology Forum 2018 “Recent Advances in Clinical & Translational Research in Neurology”
  • Int'l Joint Research / Invited
• [Presentation] MHC MATCHING IMPROVES ENGRAFTMENT OF IPSC-DERIVED NEURONS IN NON-HUMAN PRIMATES (2018)
  • Author(s): Asuka Morizane, Tetsuhiro Kikuchi, Takuya Hayashi, Hiroshi Mizuma, Sayuki Takara, Takashi Shiina, Hirohito Ishigaki, Yasushi Itoh, Keisuke Okita, Emi Yamasaki, Daisuke Doi, Hirotaka Onoe, Kazumasa Ogasawara, Shinya Yamanaka, Jun Takahashi
  • Organizer: ISSCR 2018 annual meeting
  • Int'l Joint Research
• [Presentation] Cell therapy for Parkinson’s disease with induced pluripotent stem cells (2018)
  • Author(s): Asuka Morizane
  • Organizer: THE ASIA-PACIFIC ASSOCIATION FOR NEURAL TRANSPLANTATION AND REPAIR: INAUGURAL MEETING
  • Int'l Joint Research / Invited
• [Presentation] Cell therapy for Parkinson’s disease with induced pluripotent stem cells (2018)
  • Author(s): Asuka Morizane
  • Organizer: Changing the Face of Modern Medicine: Stem Cell and Gene Therapy Organized Jointly by ESGCT, ISSCR and SFTCG
  • Int'l Joint Research / Invited
• [Presentation] Cell therapy for Parkinson’s disease with iPSCs: from bench to bed (2018)
  • Author(s): Asuka Morizane
  • Organizer: 1st NIFDS-PMDA Joint Workshop
  • Int'l Joint Research / Invited
• [Presentation] HLA-matched grafting in primates with induced pluripotent stem cells (2018)
  • Author(s): Asuka Morizane
  • Organizer: 28th Annual Meeting of the Network for European CNS Transplantation & Restoration
  • Int'l Joint Research / Invited