MECHANISM OF TRANSPLANT CHIMERISM AND SIGNIFICANCE OF MIGRATION OF DONOR-DERIVED CELLS IN ORGAN

移植嵌合机制及供体来源细胞在器官中迁移的意义

• 批准号: 05671020
• 负责人: KANEHIRO Hiromichi
• 金额: $ 1.41万
• 依托单位: NARA MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671020/
• 关键词: liver transplantation; tolerance induction; bone marrow cell; liposomal FK506; キメラ; 臓器移植; ドナー骨髄細胞

We investigated the role of donor immunocompetent cells on the tolerance induction of canine liver transplantation model. Especially, we analyzed the effect of donor bone marrow cells inoculation to the recipient at the time of liver transplantation.Outbred young adult beagle and mongrel dogs of both sexes, weighing 8-14kg were used as recipient and donor in experiment. Orthotopic canine allotransplantation of the liver was performed as our standard technique. The recipients were divided into the following groups : Group I,controls, no immunosuppression ; Group II,0.05mg/kg/day FK506 administered intravenously for 14 days postoperatively ; Group III,additional treatment of donor bone marrow inoculation at the time of transplantation in group II ; Group IV,0.05mg/kg/day of FK506 administered intravenously newly developed liposomal formulation for 14 days postoperatively. Donor bone marrow cells were obtained from donor ribs and inoculated 2X10^8 cells in recipients intravenously. The recipient survival days were evaluated in each groups.All recipients in group I died of severe acute rejection within 14 days. In group II,two of five recipients died within 2 weeks and remaining 3 recipients died of rejection on days 24,27,33, respectively. Although, recipients in group III also survived until 30-35 days after transplantation, induction of tolerance was not occurred in this experiment. However, in group IV,three of five recipients survived for more than 200 days despite discontinuation of immunosuppression on day 14.These results suggested that re-investigation of method for torelance induction by using donor bone marrow is essential and liposomal FK506 is able to reveal attractive immunosuppressive efficacy in liver transplantation.

探讨供体免疫活性细胞在犬肝移植耐受诱导中的作用。特别是分析了供体骨髓细胞在肝移植时对受体的影响。实验选用体重8~14 kg的成年成年比格犬和杂种犬作为受体和供体。我们的标准技术是进行犬的同种异体肝移植。受者分为以下几组：I组为空白对照组，II组为FK506 0.05 mg/kg/d，连续14天，II组为供体骨髓移植时加用FK506组，IV组为新研制的FK506脂质体0.05 mg/kg/d，连续14 d。供体骨髓细胞取自供体肋骨，经静脉接种2×10~(-8)细胞。观察各组受者存活天数，I组受者均于14天内死于严重急性排斥反应。II组5例受者中2例于2周内死亡，其余3例分别于第24、27、33天死于排斥反应。虽然III组的受者也能存活到移植后30-35天，但在本实验中没有发生耐受诱导。而在IV组，在第14天停止免疫抑制后，5例受者中有3例存活超过200天。这一结果表明，有必要重新研究供体骨髓诱导耐药的方法，并且脂质体FK506在肝移植中能显示出良好的免疫抑制效果。

项目成果

S.Ko, Y.Nakajima, H.Kanehiro, et al: "Significance of newly developed liposomal FK506 in canine liver transplantation" Transplantation Proceedings. 27 (1). 351-353 (1995)

S.Ko、Y.Nakajima、H.Kanehiro 等人：“新开发的脂质体 FK506 在犬肝移植中的意义”移植论文集。

S.Ko, Y.Nakajima, H.Kanehiro, et al: "The enhanced immunosuppressive efficacy of newly developed liposomal FK506 in canine liver transplantation" Transplantation. 59 (10). 1384-1388 (1995)

S.Ko、Y.Nakajima、H.Kanehiro 等人：“新开发的脂质体 FK506 在犬肝移植中增强的免疫抑制功效” 移植。

S.Ko,Y.Nakajima,H.Kanehiro,et al.: "Significance of newly developed liposomal FK506 in canine liver transplantation." Transplantation Proceedings. 27. 351-353 (1995)

S.Ko,Y.Nakajima,H.Kanehiro,et al.：“新开发的脂质体 FK506 在犬肝移植中的意义”。

S.Ko,Y.Nakajima,H.Kanehiro,et al.: "The enhanced immunosuppressive efficacy of newly developed liposamal FK506 in canine liver transplantation." Transplantation. 59. 1384-1388 (1995)

S.Ko、Y.Nakajima、H.Kanehiro 等人：“新开发的脂质体 FK506 在犬肝移植中增强的免疫抑制功效。”