Development of New Strategy of Immunological Tolerance Inductionby Intraportal administration of donor specific Mesenchymal hepatic stem cell in OrganTransplantation

器官移植中供体特异性间充质肝干细胞门静脉注射诱导免疫耐受新策略的开发

• 批准号: 21390356
• 负责人: SATO Yoshinobu
• 金额: $ 11.15万
• 依托单位: Niigata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390356/
• 关键词: 移植・再生医療; 免疫学; 外科; 免疫寛容; ドナー特異的抗原; 肝幹細胞; 移植; 臓器移植; 拒絶反応; ドナー特異的抗原門脈内投与; 調節性T細胞; shear stress

The purpose of this study was to analyze the mechanisms of theinduction of operational tolerance in clinical liver transplantation by the intra-portaladministration of donor specific antigen and make the new method of induction of toleranceby hepatic stem cell. In the basic examination, the CD133+ NCAM+ human hepaticstem/progenitor cell was recognized around the region with existence of ductular reactionin the human liver with chronic or acute hepatitis. Especially, its existence was moreclearly in the human liver with higher hepatic injury. However, it was not recognizedin the normal human liver. In the immunological analysis of intra-portal administrationof super donor antigens, the population of FoxP3^+/CD4^+CD25^+ regulatory T cells increasedin the transplant patients with no immunosuppressants.Treg. cells increased in the patients above MELD score 20. It was proved that the graspof preoperative immunological situation of transplant patients take the betteradministration of immunosuppressants.

本研究的目的是分析供者特异性抗原门静脉给药诱导临床肝移植耐受的机制，并建立肝干细胞诱导耐受的新方法。在基础检查中，在慢性或急性肝炎人肝脏中存在导管反应的区域周围识别出CD 133 + NCAM+人肝干/祖细胞。尤其是在肝损伤程度较高的人肝中，其存在更为明显。然而，它在正常人肝脏中未被识别。在门静脉注射超级供体抗原的免疫学分析中，FoxP 3 ^+/CD 4 ^+ CD 25 ^+调节性T细胞的数量在未使用免疫抑制剂的移植患者中增加。MELD评分高于20分的患者中细胞增加。说明掌握移植患者术前的免疫状况，合理使用免疫抑制剂，是提高移植患者免疫功能的有效措施。

项目成果

Total Pancreatectomy Combined with Partial Pancreas Autotransplantation for Recurrent Pancreatic Cancer: A Case Report

• DOI: 10.1016/j.transproceed.2012.03.016
• 发表时间: 2012-05-01
• 期刊: TRANSPLANTATION PROCEEDINGS
• 影响因子: 0.9
• 作者: Kobayashi, T.;Sato, Y.;Hatakeyama, K.
• 通讯作者: Hatakeyama, K.

Intra portal donorspecific antigen transfusion mightprevent re-infection of hepatitis Cvirus after living related livertransplantation in hepatitis C hepaticcirrhosis

门静脉内供体特异性抗原输注可预防丙型肝炎肝硬化活体肝移植后丙型肝炎病毒的再感染

• 发表时间: 2009
• 期刊: Hepatogastroenterology
• 作者: Sato Y;Oya H;Yamamoto S;Kobayashi T,Watanabe T;Kokai H;Yamagiwa S,Hatakeyama K
• 通讯作者: Yamagiwa S,Hatakeyama K

Impact of FoxP3+CD4+CD25+T Cells in the Recipients Acquiring Almost Tolerance

FoxP3 CD4 CD25 T 细胞对获得几乎耐受的受体的影响

• 发表时间: 2009
• 作者: Kai M;Onishi H;Katano M;et al;Yoshinobu Sato
• 通讯作者: Yoshinobu Sato

Intra portal donor specific antigen transfusion might prevent re-infecti…

门静脉内供者特异性抗原输注可能会预防再次感染……

• 发表时间: 2009
• 期刊: Hepato-Gastroenterology 56
• 作者: Y Sato;H Oya;et al
• 通讯作者: et al

Induction of operational tolerance and its mechanism by intraportal administration of donor specific antigens in living-donor liver transplantation

活体肝移植中供者特异性抗原门静脉注射诱导操作耐受及其机制

• 发表时间: 2010
• 作者: Sato Y;Yamamoto S;Oya H;et al
• 通讯作者: et al