Prevention of acute and chronic lung allograft rejection by mesenchymal stem cells

• Project/Area Number: 24592080
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Tohoku University
• Principal Investigator: OKADA Yoshinori 東北大学, 加齢医学研究所, 教授 (90323104)
• Co-Investigator(Kenkyū-buntansha): KONDO Takashi 東北大学, 加齢医学研究所, 教授 (10195901) ; SADO Tetsu 獨協医科大学, 医学部, 准教授 (20396485) ; OKOUCHI Shinya 東北大学, 医学系研究科, 講師 (40375035) ; WATANABE Tatsuaki 東北大学, 病院, 助手 (70636034) ; 大石 久 東北大学, 大学病院, 助教 (60451580)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 肺移植 / ラット / 急性拒絶反応 / 間葉系幹細胞 / リンパ球浸潤 / 浮腫 / 肺胞内出血 / サイトカイン

Outline of Final Research Achievements

We examined the effects of human mesenchymal stem cells (hMSCs) that exhibit immunomodulatory and anti-inflammatory effects on acute allograft rejection in a highly allogeneic lung transplantation model. The lung allografts were harvested on day 6 after transplantation and submitted to the pathological examination and RT-PCR analysis. The stage of acute rejection and pathological scores of lymphocytic infiltration, edema and intraalveolar hemorrhage of the allograft in the recipients administered with hMSCs were significantly decreased compared with those in the control animals receiving PBS. Gene expression of TNF-α in the allografts in the hMSC groups showed a trend toward decrease compared with the those in the control group. The present study demonstrated that hMSC administration was effective in preventing acute allograft rejection in a rat model of lung transplantation.

Research Products

• [Presentation] Human mesenchymal stem cells reduced acute inflammation associated with acute allograft rejection in a rat model of lung transplantation.
  • Author(s): 3. Ishibashi N, Okada Y, Watanabe Y, WatanabeT, Hoshikawa Y, Kondo T
  • Organizer: The 13th Congress of the Asian Society of Transplantation
  • Place of Presentation: Kyoto
• [Presentation] 間葉系幹細胞投与による肺移植後急性拒絶反応抑制に関する実験的検討
  • Author(s): 石橋 直也、岡田 克典、渡辺 有為、渡邉 龍秋、江場 俊介、野津田 泰嗣、 星川 康、近藤 丘
  • Organizer: 第29回日本肺および心肺移植研究会
  • Place of Presentation: 千葉