The suppressive mechanism of liver immune reactivity after islet transplantation by mesenchymal stem cells

• Project/Area Number: 25461948
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: Ishiyama Kohei 広島大学, 大学病院, 病院助教 (50437589)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 糖尿病 / 移植 / 免疫 / 免疫学 / 膵島移植 / NK細胞 / 間葉系幹細胞

Outline of Final Research Achievements

Islet transplantation is considered as one of the standard therapy against type 1 diabetes melitus. The purpose of this study is to develop a new immunesuppressant treatment for improvement of islet graft engraftment by regulation of liver immune response after islet transplantation.
We confirmed that cytotoxic activity of natural killer (NK) cells in the liver were increased after intraportal islet transplantation and activation of NK cells prevent islet graft better engraftment in the murine model. In this study, we focused on the mesenchymal stem cells (MSCs) which possess the immune suppressive function for suppression of the NK cells activation after ielet transplantation. The simultaneous administration of MSCs with islet into the portal vein showed prolonged islet graft survival and the suppressive effect of activated liver NK cells after islet transplantation when compared with islet transplantation alone.

Research Products

• [Presentation] 膵島移植後における肝臓内NK細胞免疫応答の経時的変化 (2016)
  • Author(s): 佐伯吉弘
  • Organizer: 第43回日本膵膵島移植研究会
  • Place of Presentation: 広島
  • Year and Date: 2016-03-04
• [Presentation] 骨髄由来間葉系幹細胞による膵島移植後、肝臓内NK細胞傷害活性抑制効果 (2016)
  • Author(s): 石田 伸樹
  • Organizer: 第43回日本膵膵島移植研究会
  • Place of Presentation: 広島
  • Year and Date: 2016-03-04
• [Presentation] 骨髄由来間葉系幹細胞を用いた膵島に対する肝臓内NK細胞傷害活性抑制の試み (2015)
  • Author(s): 石田 伸樹
  • Organizer: 第42回日本臓器保存生物医学会学術集会
  • Place of Presentation: 盛岡
  • Year and Date: 2015-11-13
• [Presentation] Liver-resident natural killer cells exposed to instant blood-mediated inflammatory reaction after intraportal islet transplantation persistently sustain memory phenotype with cytotoxicity against islets (2015)
  • Author(s): Saeki Y
  • Organizer: TSS2015 14th Transplantation Science Symposium
  • Place of Presentation: Lorne, Australia
  • Year and Date: 2015-11-11
  • Int'l Joint Research
• [Presentation] 肝臓内NK細胞の移植膵島に対する継時的な免疫応答変化と機能解析 (2015)
  • Author(s): 佐伯吉弘
  • Organizer: 第51回日本移植学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-10-01
• [Presentation] 骨髄由来間葉系幹細胞移植による膵島グラフト傷害に対する肝臓内NK細胞活性抑制機構の解明 (2015)
  • Author(s): 石田 伸樹
  • Organizer: 第51回日本移植学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2015-10-01
• [Presentation] 肝臓内memory NK細胞による移植後膵島グラフトに対する免疫応答機構の解明 (2015)
  • Author(s): 佐伯吉弘
  • Organizer: 第70回日本消化器外科学会総会
  • Place of Presentation: 浜松
  • Year and Date: 2015-07-15
• [Presentation] 膵島移植における肝臓内memory NK細胞の 免疫応答機構の解明 (2015)
  • Author(s): 佐伯吉弘
  • Organizer: 第46回日本膵臓学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-06-19
• [Presentation] Persistent expansion of DX5- memory natural killer cells in the liver after intraportal islet transplantation. (2015)
  • Author(s): Saeki Y
  • Organizer: American Transplant Congress 2015
  • Place of Presentation: Philadelphia, America
  • Year and Date: 2015-05-02
  • Int'l Joint Research
• [Presentation] Mesenchymal stem cells suppress cytotoxicity of activated natural killer cells in liver via the TRAIL-TRAIL receptor pathway in islet transplantation (2015)
  • Author(s): Ishida N
  • Organizer: American Transplant Congress 2015
  • Place of Presentation: Philadelphia, America
  • Year and Date: 2015-05-02
  • Int'l Joint Research
• [Presentation] 膵島移植後早期から長期にかけて肝臓内memory NK細胞がグラフトに与える免疫応答機構の解析 (2015)
  • Author(s): 佐伯 吉弘、石山宏平
  • Organizer: 日本膵・膵島移植研究会
  • Place of Presentation: 東京
  • Year and Date: 2015-03-06 – 2015-03-07
• [Presentation] 膵島保護へむけた膵島移植における肝臓内Natural Killer細胞活性化機構の解明 (2014)
  • Author(s): 佐伯 吉弘、石山宏平
  • Organizer: 日本臓器保存生物医学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-11-28 – 2014-11-29
• [Presentation] 膵島移植後におけるIBMIRを介した肝臓内NK細胞活性化メカニズムの解析 (2014)
  • Author(s): 佐伯 吉弘、石山宏平
  • Organizer: 日本移植学会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-10 – 2014-09-12
• [Presentation] Liver DX5- natural killer cells play a crucial role on the instant blood-mediated inflammatory reaction after islet transplantation (2014)
  • Author(s): 佐伯 吉弘、石山宏平
  • Organizer: American Transplant Congress
  • Place of Presentation: サンフランシスコ、USA
  • Year and Date: 2014-07-26 – 2014-07-31
• [Presentation] 膵島移植後グラフト傷害に対する肝臓内Memory Natural killer細胞の機能解析 (2014)
  • Author(s): 佐伯 吉弘、石山宏平
  • Organizer: 日本消化器外科学会
  • Place of Presentation: 福島
  • Year and Date: 2014-07-16 – 2014-07-18
• [Presentation] 膵島移植のInstant blood―mediated inflammatory reaction（IBMIR）環境下におけるNatural Killer（NK）細胞の活性化機構の解明 (2014)
  • Author(s): 佐伯 吉弘、石山宏平
  • Organizer: 日本外科学会
  • Place of Presentation: 京都
  • Year and Date: 2014-04-03 – 2014-04-05
• [Presentation] 膵島移植後のInstant blood-mediated inflammatory reaction環境下における肝臓内Memory Natural Killer細胞の活性化機構の解明 (2014)
  • Author(s): 石山宏平、佐伯吉弘、平田文宏、田中友加、大段秀樹
  • Organizer: 日本膵・膵島移植研究会
  • Place of Presentation: 名古屋
• [Presentation] 膵島移植後グラフト傷害に対する肝臓内Memory Natural killer細胞の機能解析 (2013)
  • Author(s): 佐伯吉弘、石山宏平、平田文宏、田中友加、大段秀樹
  • Organizer: 日本消化器外科学会
  • Place of Presentation: 宮崎
• [Presentation] Mesenchymal Stem Cells Suppress Cytotoxic Activity of Natural Killer Cells in Islet Cell Transplantation (2013)
  • Author(s): Y. Saeki, K. Ishiyama, F. Hirata, Y. Tanaka, H. Ohdan
  • Organizer: American Transplant Congress
  • Place of Presentation: シアトル、USA