权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Research for immuno-logical tolerance induction in islet xeno-transplantation -Therapeutic effect of a adenovirus or retrovirus mediated CTLA4Ig gene transfer combined with immunosuppressive regents-

胰岛异种移植中免疫耐受诱导的研究-腺病毒或逆转录病毒介导的CTLA4Ig基因转移联合免疫抑制药物的治疗效果-

基本信息

批准号：
13671233
负责人：
NAKATA Seizou
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671233/
关键词：
Islet adenoviral vector CTLA4Ig FK506 CTL4Ig

项目摘要

【 Background & Aims 】 Adenovirus-mediated CTLA4Ig gene transfer has been reported to enhance graft survival in several rodent vansplantation models. In this study, we investigated the efficacy of ex vivo and systemic transfer of the CTLA4Ig gene by adenoviral vectors in pancreatic islet allo-transplantation.【Methods】 Islet grafts from BN rats were transplanted to chemically induced diabetic LEW rats. First, ex vivo CTLA4Ig gene transfer into isolated islets was performed prior to transplantation. Secondly, systemic gene transfer was accomplished by intravenous administration immediately after the transplantation procedure.【 Results 】 Survival of transduced grafts under the kidney capsule was slightly prolonged (8.6±1.3 days) compared with survival of untransduced grafts (6.7±1.2 days); when combined with a short course of FK506, graft survival was further extended (32.6±10.7 days vs. 13.7±1.0 days with FK506 alone).In systemically transduced animals, islet grafts under the kidney capsule survived longer (15.2±3.3 days) than in controls (6.7±1.2 days) , and when FK506 was administered perioperatively, all the islet grafts survived for more than 100 days. Finally, the LEW recipients with long-surviving islet were re-transplanted with islet grafts from the same donor strain (BN) on day 100. However, the second islet grafts consistently failed in the recipients.【Conclusions】 We conclude that in this transplant model, CTLA4Ig gene transfer and FK506 treatment synergistically improved islet graft survival, systemic transfer of the gene was more effective than ex vivo transfer to the islets, and donor-specific tolerance could not be achieved for islet transplantation.

[背景与目的]腺病毒介导的CTLA4Ig基因转移可在多种啮齿动物移植模型中提高移植物存活率。本研究对腺病毒载体介导CTLA4Ig基因在同种异体胰岛移植中的体外和系统转移效果进行了研究。首先，在移植前将CTLA4Ig基因体外转移到分离的胰岛中。[结果]转导肾被膜下移植物存活时间(8.6±1.3)d较未转导移植物存活(6.7±1.2)d略有延长；与短程FK506联合应用，移植物存活时间进一步延长(32.6±10.7天比13.7±1.0天)。在系统转导的动物中，肾被膜下胰岛移植物存活时间(15.2±3.3天)长于对照组(6.7±1.2天)，而围手术期应用FK506时，所有移植物存活时间均超过100天。最后，长期存活胰岛的LEW受体在第100天再次移植相同供体品系(BN)的胰岛。结论在此移植模型中，CTLA4Ig基因转移和FK506治疗能协同提高胰岛移植物的存活率，系统转移的胰岛移植物比体外转移的胰岛移植物更有效，胰岛移植不能达到供体特异性耐受。