Development of therapy of Alzheimers disease with iPS cell-derivedmacrophages

• Project/Area Number: 23659158
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General medical chemistry
• Research Institution: Kumamoto University
• Principal Investigator: SENJU Satoru 熊本大学, 大学院・生命科学研究部, 准教授 (50274709)
• Research Collaborator: TAKAMATSU Koutaro 熊本大学, 大学院・生命科学研究部, 大学院・・生、医員
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アルツハイマー病 / iPS 細胞 / マクロファージ / アミロイドβ / iPS細胞 / 治療 / 細胞治療 / アミロイドベータ / 疾患モデルマウス

Research Abstract

The purpose of this study is to generate macrophages with acapacity to degrade or remove amyloid-・protein, which is known to be the causative agentof Alzheimer ’ s disease.Before this project, we had established a technology to generate functionalphagocytes (macrophages) from mouse and human iPS cells. In the current study , wegenerated macrophages expressing Fc-receptor-fused form of single chain antibody specificto amyloid-・. In addition, we made macrophages expressing neprilysin, a protease reportedto be highly potent in degradation of amyloid-・. We administered the genetically modifiediPS cell-derived macrophages into model mice of Alzheimer ’ s disease, and evaluate whetherthey could reduce the level of amyloid-・in vivo.

Research Products

• [Journal Article] Generation of dendritic cells and macrophages from human induced pluripotent stem cells aiming at cell therapy (2011)
  • Author(s): Senju, S., Haruta, M., Matsumura, K., Matsunaga, Y., Fukushima, S., Ikeda, T., Takamatsu, K., Irie, A., Nishimura, Y.
  • Journal Title: Gene Therapy Volume: 18 Issue: 9 Pages: 874-883
  • DOI: 10.1038/gt.2011.22
  • Peer Reviewed
• [Journal Article] Immunotherapy with pluripotent stem cell-derived dendritic cell (2011)
  • Author(s): Senju, S., Matsunaga, Y., Fukushima, S., Hirata, S., Motomura, Y., Fukuma, D., Matsuyoshi, H., Nishimura, Y.
  • Journal Title: Seminars in Immunopathology Volume: 33 Issue: 6 Pages: 603-612
  • DOI: 10.1007/s00281-011-0263-y
  • NAID: 120005199485
  • Peer Reviewed
• [Presentation] iPS細胞を用いたがんに対する免疫細胞療法 (2011)
  • Author(s): 千住 覚
  • Organizer: 第24回日本バイオセラピィ学会学術集会総会(招待講演)
  • Place of Presentation: ダイワロイネットホテル和歌山