The effect of therapeutic angiogenesis using by CD11b+ cells transplantation in a murine model of hind limb ischemia

• Project/Area Number: 26870785
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine; Cardiovascular surgery
• Research Institution: Fukuoka University
• Principal Investigator: Nishinakamura Hitomi 福岡大学, 医学部, 助教 (90597692)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: 虚血肢 / マクロファージ / 血管再生 / 細胞治療 / 細胞移植

Outline of Final Research Achievements

The use of cultured BMCs can reduce the total number of injections required and were shown to induce therapeutic angiogenesis in a murine model of hind limb ischemia. Angiogenesis, lymphangiogenesis, and blood flow recovery ratio were significantly higher in the GM-CSF-cultured F4/80+ macrophage (GM-Macrophage)-treated group compared with controls. Furthermore, Foxp3+ cell numbers and tissue IL-10 concentrations were significantly increased compared with controls. There was no significant difference in blood flow recovery between GM-Macrophage and M-CSF-cultured F4/80+ macrophages (M-Macrophage). Thus, GM-Macrophage were associated with improved blood flow in hind limb ischemia similar to M-Macrophage. The selective methods of culturing and treating GM-Macrophage cells similar to M-Macrophage cells could be used clinically as a novel cell therapy for critical limb ischemia.

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
• [Journal Article] Pretreatment of donor islets with papain improves allograft survival without systemic immunosuppression in mice. (2016)
  • Author(s): Kumano K, Nishinakamura H, Mera T, Itoh T, Takahashi H, Fujiwara T, Kodama S.*
  • Journal Title: Islets Volume: 8(5) Issue: 5 Pages: 145-155
  • DOI: 10.1080/19382014.2016.1223579
  • Peer Reviewed
• [Journal Article] Islet-derived damage-associated molecular pattern molecule contributes to immune responses following microencapsulated neonatal porcine islet xenotransplantation in mice. (2016)
  • Author(s): Itoh T, Hata Y, Nishinakamura H, Kumano K, Takahashi H, Kodama S.*
  • Journal Title: Xenotransplantation Volume: 23(5) Issue: 5 Pages: 393-404
  • DOI: 10.1111/xen.12253
  • Peer Reviewed
• [Journal Article] M-CSF treated F4/80+ BMCs improve murine hind limb ischemia similar to M-CSF differentiated macrophages. (2014)
  • Author(s): Kuwahara G., Nishinakamura H., Kojima D, Tashiro T., *Kodama S.
  • Journal Title: PLOS ONE Volume: 9 Issue: 9 Pages: e106987-e106987
  • DOI: 10.1371/journal.pone.0106987
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 極性を有するマクロファージ投与によるマウス虚血肢血流改善効果におけるIL-10の作用機序の解析 (2017)
  • Author(s): 西中村瞳、秦優子、高橋宏幸、伊東威、小玉正太
  • Organizer: 第16回日本再生医療学会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-07
• [Presentation] 虚血肢マウスを用いた細胞治療におけるIL-10の作用機序の解析 (2016)
  • Author(s): 西中村瞳，秦優子，熊野健二郎，髙橋宏幸，伊東威，岩本隆宏，小玉正太
  • Organizer: 第15回日本再生医療学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2016-03-17
• [Presentation] M-CSF あるいは GM-CSF培養F4/80陽性細胞投与によるマウス虚血肢モデルを用いた血流改善効果の比較検討 (2015)
  • Author(s): 西中村瞳, 桑原豪, 小島大望, 伊東威, 田代忠, 小玉正太
  • Organizer: 第14回日本再生医療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] M1 macrophages induce therapeutic improvements in a murine model of hind limb ischemia similar to M2 macrophages (2014)
  • Author(s): Nishinakamura,H., Kuwahara,G., Kojima,D., Tashiro,T., Kodama,S.
  • Organizer: TERMIS EU Meeting 2014
  • Place of Presentation: Genova, Italian Republic
  • Year and Date: 2014-06-10 – 2014-06-13