Semimature dendritic cells inducing tolerance in allotransplantation of hepatocytes differentiated from mouse embryonic stem cells
Semimature dendritic cells inducing tolerance in allotransplantation of hepatocytes differentiated from mouse embryonic stem cells
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DOI：
10.3760/cma.j.issn.1001-9030.2012.11.022
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发表时间：
2012-11
期刊：
影响因子：
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通讯作者：
A. Hu;H. Xiaoshun
中科院分区：
文献类型：
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作者：
A. Hu;H. Xiaoshun
目的探讨半成熟树突状细胞（smDC）诱导小鼠胚胎干细胞（ESCs）分化为肝细胞移植耐受的可行性。方法将绿色荧光蛋白（GFP）标记的129只小鼠D3-ESCs体外诱导分化为肝细胞，并将其分化为髓样smDC。BALB/C小鼠（受体）首先注射smDC（1.0 × 105个细胞/只），3天后，将129只小鼠中的D3-ESCs分化的肝细胞作为细胞悬液注入BALB/C小鼠肝被膜中（2.0 × 106个细胞/只），然后对移植肝细胞进行组织病理学检查，并测定血清ALT、总胆红素（TB）和移植肝细胞存活率。采用酶联免疫吸附法（ELISA）检测受体血清IL-2、IL-10水平。BALB/C小鼠接受129只小鼠smDC后，移植物存活时间延长，CD 4+淋巴细胞浸润明显减少，血中IL-10、IL-20水平明显升高，而CD 4+淋巴细胞浸润明显减少，血中IL-20、IL-20水平明显升高，与对照组相比，差异有统计学意义（P < 0.05）。smDC组10例明显高于对照组而IL-2水平则低于对照组（P < 0.05（P < 0.05），免疫组化结果显示，移植细胞与受体细胞排列整齐，表达白蛋白。在同种异体ESC-肝细胞移植中，smDCs可诱导部分免疫耐受，供体smDCs预处理受体可促进ESC-肝细胞移植。关键词：树突状细胞;胚胎干细胞;肝细胞移植;移植耐受
Objective To induce tolerance in transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) by using semimature dendritic cells (smDCs).Methods Green fluorescent protein (GFP)-stained D3-ESCs in the 129 mice were differentiated into hepatocytes by methods we previously reported.Myeloid smDCs were derived from the 129 mice in vitro also as we previously reported.Then,BALB/C mice (recipients) were firstly injected with smDCs (1.0 × 105 cells per mouse).Three days later,hepatocytes differentiated from D3-ESCs in the 129 mice as cell suspension were poured into BALB/C mice liver capsule (2.0 × 106 cells per mouse).Thereafter,histopathological examinations of the hepatocytes graft were performed.The serum ALT,total bilirubin (TB) and the survival rate of hepatocytes graft were also determined.At the same time,the levels of IL-2 and IL-10 in the recipients were measured by enzyme linked immunosorbent assay (ELISA).Results As compared with control group,the survival time of the allograft of D3-ESC-hepatocytes was prolonged when BALB/C mice received the 129 mice smDCs.CD4+ lymphocytes infiltration was significantly reduced in smDC group.The blood levels of IL-10 in smDC group were significantly higher than those in control group (P ＜ 0.05),but those of IL-2 in smDC group were lower than those in control group (P ＜ 0.05).Moreover,pathological examination demonstrated that transplanted cells and recipient cells were well arranged and express albumin in smDC group.Conclusion Donor smDCs could induce partly tolerance in allotransplantation of ESC-hepatocytes.Pre-treatment of recipients with donor smDCs has potential for ESC-derived cells allotransplantion. Key words: Dendritic cell; Embryonic stem cell; Hepatocyte ransplantation; Transplantation tolerance