| Project/Area Number |
15K15472
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岩崎 研太 愛知医科大学, 医学部, 准教授 (10508881)
大西 彰 日本大学, 生物資源科学部, 教授 (30414890)
三輪 祐子 愛知医科大学, 医学部, 助教 (90572941)
中井 美智子 国立研究開発法人農業・食品産業技術総合研究機構, 生物機能利用研究部門, 研究員 (30442825)
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| Research Collaborator |
FUCHIMOTO Daiichiro
SUZUKI Shunichi
YAMAMOTO Takayuki
OKADA Manabu
TAKEDA Asami
HIRAMITSU Takahisa
KITAGAWA Hitoshi
IMAEDA Noriaki
HANEDA Masataka
HORIMI Kosei
MATSUOKA Yutaka
MAENAKA Akihiro
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 移植・再生医療 / ABO血液型不適合 / HLA抗体 / 抗体陽性腎移植 / モデルブタ / 遺伝子 / 抗体陽性移植 / ABO血液型抗体 / 腎移植 / ABO不適合 |
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| Outline of Final Research Achievements |
Control of antibody-mediated rejection caused by blood group ABO or HLA-incompatibility is essential for long-term graft survival after organ transplantation. Blood group A or B transferase and fucosyltransferase (FUT1) were transfected into two types of Duroc fibroblasts (non-A). We attempted to produce cloned pig expressing blood group A or B.
Subclass IgG4 and RNA interference were effective for reducing antibody-mediated, complement dependent cytotoxicity. Acute antibody-mediated rejection after ABO-incompatible renal transplantation was associated with pre-transplant IgG1,IgG2, IgG3 and C1q binding capacity. Microarray analysis using graft biopsy revealed that ABO-incompatibility could increase BACH1 gene and decrease reactive oxygen species. Anti-A/B antibody binding to endothelial cells induced the resistance to antibody-mediated, complement-dependent cytotoxicity due to downregulation of HLA-DR expression and upregulation of complement regulatory proteins (CD55 and CD59).
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