The therapy of autoimmune disease by ES cell-derived myeloid cells (ES-ML)

• Project/Area Number: 15K19493
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kumamoto University
• Principal Investigator: Ikeda Tokunori 熊本大学, 医学部附属病院, 助教 (00613530)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ES細胞由来ミエロイド細胞 / iPS細胞由来ミエロイド細胞 / 実験的自己免疫性脳脊髄炎 / 免疫抑制性マクロファージ / ES細胞由来ミエロイド細胞 (ES-ML) / iPS細胞由来ミエロイド細胞 (iPS-ML) / 実験的自己免責性脳脊髄炎 (EAE) / 免疫制御 / 細胞治療療法 / 自己免疫疾患 / 自己免疫疾患モデルマウス / EAE

Outline of Final Research Achievements

I investigated whether or not ES or iPS cell derived myeloid cell (ES-, iPS-ML) had the immunoinhibitory function for experimental autoimmune encephalomyelitis (EAE). The administration of TARIL, which function immuno-inhibitory molecule, gene transferred ES-ML (ES-ML-TRAIL) improved the clinical symptoms of EAE. However, a lot of ES-ML-TRAIL were needed to ameliorate the state of EAE. On the other hand, ES- or iPS-ML functioned like a macrophage, and expressed immunoinhibitory macrophage’s marker, CD163 and CD206. These results suggested the possibility that the application of ES- or iPS-ML was appropriate in the diseases that macrophage’s function were available, but autoimmune diseases.

Research Products

• [Journal Article] Soluble IL-6R expressed by myeloid cells reduces tumor-specific Th1 differentation and drives tumor progression (2017)
  • Author(s): Tsukamoto H, Fujieda K, Hirayama M, Ikeda T, Yuno A, Matsumura K, Fukuma D, Araki K, Mizuta H, Nakayama H, Senju S, Nishimura Y
  • Journal Title: Cancer Research Volume: 14 Issue: 9 Pages: 2279-2291
  • DOI: 10.1158/0008-5472.can-16-2446
  • Peer Reviewed / Open Access
• [Journal Article] Therapy of primary and metastatic liver cancer by human iPS cell-derived myeloid cells producing interferon-β. (2017)
  • Author(s): Sakisaka M, Haruta M, Komohara Y, Umemoto S, Matsumura K, Ikeda T, Takeya M, Inomata Y, Nishimura Y, Senju S.
  • Journal Title: J Hepato-Biliary-Pancreatic Sciences. Volume: - Issue: 2 Pages: 109-119
  • DOI: 10.1002/jhbp.422
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Novel antibody for the treatment of transthyretin amyloidosis. (2016)
  • Author(s): Hosoi A, Su Y, Torikai M, Jono H, Ishikawa D, Soejima K, Higuchi H, Guo J, Ueda M, Suenaga G, Motokawa H, Ikeda T, Senju S, Nakashima T, Ando Y
  • Journal Title: J Biol Chem Volume: 25 Issue: 48 Pages: 25096-25105
  • DOI: 10.1074/jbc.m116.738138
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Involvement of macrophages in the pathogenesis of familial amyloid polyneuropathy and efficacy of human iPS cell-derived macrophages in its treatment. (2016)
  • Author(s): Suenaga G, Ikeda T, Komohara Y, Takamatsu K, Kakuma T, Tasaki M, Misumi Y, Ueda M, Ito T, Senju S, Ando Y
  • Journal Title: PLoS One Volume: 11 Issue: 10 Pages: e0163944-e0163944
  • DOI: 10.1371/journal.pone.0163944
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Generation of Large Numbers of Antigen-Expressing Human Dendritic Cells Using CD14-ML Technology (2016)
  • Author(s): Yuya Imamura, Miwa Haruta, Yusuke Tomita, Keiko Matsumura, Tokunori Ikeda, Akira Yuno1, Masatoshi Hirayama, Hideki Nakayama, Hiroshi Mizuta, Yasuharu Nishimura, Satoru Senju
  • Journal Title: Plos One Volume: 11 Issue: 4 Pages: e0152384-e0152384
  • DOI: 10.1371/journal.pone.0152384
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 大量培養可能なES細胞由来ミエロイド細胞 (ES-ML)を利用した自己免疫疾患モデルマウスの治療 (2017)
  • Author(s): 池田徳典
  • Organizer: 日本内科学会
  • Place of Presentation: 東京、東京国際フォーラム