The examination of blood flow improvement effect in murine model of hindlimb ischemia by administration of polar macrophages

• Project/Area Number: 17K18299
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular surgery; Cardiovascular medicine
• Research Institution: National Cancer Center Japan
• Principal Investigator: Hitomi NISHINAKAMURA 国立研究開発法人国立がん研究センター, 研究所, 特任研究員 (90597692)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: マクロファージ / 血管新生 / リンパ管新生 / 虚血肢 / 細胞治療 / IL-10 / 重症虚血肢

Outline of Final Research Achievements

IL-10 KO M-Mφ was used to elucidate the mechanism of action of improving blood flow in hind limb ischemia by administration of M-Mφ cultured in the presence of M-CSF. IL-6 protein shows significantly higher values in the affected side after WT M-Mφ administration than in the non-administered cells and IL-10 KO M-Mφ-administered groups, and IL-10 produced by the administered cells may regulate the expression of IL-6 protein. Next, in vitro evaluation of angiogenesis and lymphangiogenesis was carried out in a co-culture system. As a result, co-culture with IL-10 KO M-Mφ showed a decrease the formation of lymphatic endothelial cells. From these results, it was suggested that IL-10 expressed in the treated cells was involved.

Academic Significance and Societal Importance of the Research Achievements

細胞移植による血管再生治療は重症下肢虚血における重要な治療戦略であるが、投与細胞群による虚血肢の細胞が受ける影響及び血管・リンパ管新生に対する作用機序は不明な点が多い。これまでに我々はM-CSF存在下で培養したF4/80陽性細胞 (M-Mφ) 投与による虚血肢血流改善効果を見出してきたが、本研究ではIL-10 KO M-Mφを用いることにより細胞治療におけるIL-10の重要性を明らかにした。

Research Products

• [Journal Article] The spleen is an ideal site for inducing expansion of transplanted islet grafts in mice (2017)
  • Author(s): Itoh T, Nishinakamura H, Kumano K, Takahashi H, Kodama S.*
  • Journal Title: PLoS One Volume: 12(1) Issue: 1 Pages: e0170899-e0170899
  • DOI: 10.1371/journal.pone.0170899
  • Peer Reviewed / Open Access
• [Presentation] マクロファージ投与による虚血肢マウス血流改善効果の作用機序 (2017)
  • Author(s): 西中村瞳、秦優子、高橋宏幸、松岡泰祐、桑原豪、伊東威、吉松軍平、小玉正太
  • Organizer: 第17回日本再生医療学会
• [Book] 移植 (2017)
  • Author(s): 西中村 瞳、伊東 威、小玉 正太
  • Total Pages: 5
  • Publisher: 日本移植学会
• [Book] 細胞 (2017)
  • Author(s): 西中村 瞳、伊東 威、吉松 軍平、小玉 正太
  • Total Pages: 4
  • Publisher: 北隆社 ニュー・サイエンス社