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学科主题基础医学
Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts
Jin, YZ; Zhang, QY; Xie, SS
刊名TRANSPLANTATION PROCEEDINGS
2003-12-01
DOI10.1016/j.transproceed.2003.10.025
35期:8页:3156-3159
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Immunology ; Surgery ; Transplantation
研究领域[WOS]Immunology ; Surgery ; Transplantation
关键词[WOS]TOLERANCE ; INDUCTION
英文摘要

Co-stimulatory blockade combined with donor bone marrow transfusion engenders stable mixed chimerism and robust tolerance to various organ and cell transplants. However, repeated administration of costly agents to block the co-stimulatory pathway and the high doses of donor bone marrow cells (BMCs) used in most protocols are impeding clinical development of this strategy. To circumvent these shortcomings, we developed a plan in which repeated administration of costly agents was replaced by a single injection of adenovirus containing the gene of interest, and the high dose of donor BMCs replaced by a mixture of low-dose donor BMCs and splenocytes (SPLCs). Cardiac allografts from DA(RT- 1(a)) rats were transplanted heterotopically into the abdomens of LEW(RT-1(1)) rats. A cocktail of adenovirus containing CTLA4Ig gene (AdCTLA4Ig), donor BMCs (100 X 10(6)), and SPLCs (50 X 10(6)) was administered to recipients via the portal vein immediately after grafting (n = 6). Treatment with regimens, including AdCTLA4Ig only, AdCTLA4Ig plus donor BMCs, and AdCTLA4Ig plus donor SPLCs, significantly prolonged cardiac allograft survival in recipient rats, while animals that received no treatment or treatment with control adenovirus (AdLacZ) promptly rejected their allografts. Nevertheless, LEW recipients treated with AdCTLA4Ig and the mixture of a low dose of donor BMCs and SPLCs developed stable mixed chimerism, rendering them long-term survivors of cardiac allografts that also accepted skin grafts from the donor but not the third-party strain. We conclude that blockade of CD28-B7 pathway with AdCTLA4Ig plus a mixture of low doses of donor BMCs and SPLCs is a feasible strategy to induce long-term mixed chimerism with a potential application for clinical development.

语种英语
WOS记录号WOS:000187576900085
引用统计
被引频次:3[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57919
专题北京大学基础医学院_免疫学系
作者单位Peking Univ, Ctr Hlth Sci, Dept Immunol, Beijing 100083, Peoples R China
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GB/T 7714
Jin, YZ,Zhang, QY,Xie, SS. Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts[J]. TRANSPLANTATION PROCEEDINGS,2003,35(8):3156-3159.
APA Jin, YZ,Zhang, QY,&Xie, SS.(2003).Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts.TRANSPLANTATION PROCEEDINGS,35(8),3156-3159.
MLA Jin, YZ,et al."Low-dose donor bone marrow cells and splenocytes plus adenovirus encoding for CTLA4Ig gene promote stable mixed chimerism and long-term survival of rat cardiac allografts".TRANSPLANTATION PROCEEDINGS 35.8(2003):3156-3159.
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