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半成熟树突状细胞与Tregs水平对ESCs分化的肝细胞移植小鼠模型免疫耐受的影响
  • ISSN号:0376-2491
  • 期刊名称:《中华医学杂志》
  • 时间:0
  • 分类:R733.71[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]中山大学附属第一医院广东省器官捐献与移植免疫重点实验室广东省器官移植国际科技合作基地,广州510080, [2]中山大学干细胞与组织工程研究中心
  • 相关基金:国家自然科学基金(81672998,81371693,81172831);广东省科技计划项目(20138010404016,20128031800257,2013/7051000020);广东省自然科学基金($2013010015935);广东省器官捐献与移植免疫重点实验室基金(2013A061401007);广东省器官移植国际科技合作基地项目(20158050501002);广州市产学研协同创新重大专项(2060404,2014Y2-00114)
中文摘要:

目的观察半成熟树突状细胞(smDCs)在小鼠胚胎干细胞(ESCs)来源的肝细胞移植中诱导免疫耐受的作用及机制,并分析smDCs与调节性树突状细胞(regDCs)之间的关系。方法将绿色荧光蛋白(GFP)标记的129系小鼠ESCs按前期方法向肝细胞诱导分化,同时诱导129系小鼠骨髓单核细胞向smDCs和regDCs分化。将smDCs、regDCs分别预先输入BALB/c小鼠体内,3d后再将ESCs分化的肝细胞移植入BALB/e小鼠肝实质内。观察移植细胞生存时间、生长状况、局部免疫反应情况;检测分析受体血CD4+T细胞Foxp3表达情况等。结果对照组小鼠肝实质内移植细胞仅生存1周,smDCs组与regDCs组生存时间可达4周,移植部位CD3+T细胞浸润较对照组明显减轻;smDCs与regDCs在形态和表型方面相似,二者均中度表达MHC-11、CIMO、CD80、CD86;smDCs组受体小鼠外周血CD4+T细胞Foxp3表达量明显升高由1.11%上升至5.38%;regDCs组Foxp3表达量亦有所升高达3.87%。结论smDCs能诱导ESCs源性肝细胞移植耐受,其机制可能与Foxp3+ Tregs产生相关。smDCs与regDCs作用类似,且均中度表达MHC.Ⅱ、CD40等,推测为同一类型的耐受性树突状细胞。

英文摘要:

Objective To investigate the inducing effect and mechanism of semimature dendritic cell (smDCs) on transplantation tolerance of hepatocytes differentiated from mouse embryonic stem cells (ESCs), and to study the connections between smDCs and regulatory dendritic cells (regDCs). Methods ESCs of 129 mouse labelled green fluorescent protein (GFP) were induced to hepatocytes by using previous methods. Meanwhile, bone marrow mononuclear cells of 129 mouse were induced to smDCs and regDCs. Moreover, the hepatocytes differentiated from 129 mouse ESCs were transplanted into liver of BALB/e mouse 3 days after infusing smDCs and regDCs suspension of 129 mouse into BALB/c mouse by tail vein respectively. After that, the growth status and survival time of transplanted cells in the recipient and infiltration of lymphocytes in transplant sites were observed. Furthermore, Foxp3 expression of peripheral blood CD4 + T cells was also tested. Results In the control group, the transplanted cells in liver of BALB/c mouse survived only about 1 week. In contrast, the transplanted cells of smDC groups and regDCs groups survived about 4 weeks and the transplant sites of smDC groups also had less CD3 + T cells. The morphology of smDCs were similar with regDCs. The expression of MHC-Ⅱ , CD40, CD80 and CD86 on smDCs and regDCs were moderate. Moreover, the Foxp3 expression of peripheral blood CD4 + T cells in smDC groups was higher than that in the control groups, from 1.11% up to 5.38%. The Foxp3 expression in regDC groups rose to 3, 87%. Conclusion The smDCs could induce transplantation tolerance of hepatocytes differentiated from 129 mouse ESCs in the recipient. The mechanism was associated with high level of Foxp3 + Tregs, which could be increased by means of smDCs appropriate expression of MHC-Ⅱ , CD4O, CD80 and CD86. The smDCs and regDCs were the same type of tolerance dendritic cells.

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期刊信息
  • 《中华医学杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市东四西大街42号
  • 邮编:100710
  • 邮箱:nmjc@cma.org.cn
  • 电话:010-85158355 85158180
  • 国际标准刊号:ISSN:0376-2491
  • 国内统一刊号:ISSN:11-2137/R
  • 邮发代号:2-588
  • 获奖情况:
  • 1992年与1996年连续两次在中宣部、国家科委、新闻...,1999年、2003年分别荣获首届国家期刊奖和第二届国...,中国期刊方阵“双高”期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,荷兰医学文摘,美国生物医学检索系统,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:101941