胎肝细胞移植治疗粘多糖贮积症的实验研究

山东大学学报(医学版) ›› 2009, Vol. 47 ›› Issue (11): 59-63.

胎肝细胞移植治疗粘多糖贮积症的实验研究

刘晓莉，万江波，梁辉

上海交通大学医学院附属新华医院血液科，上海 200092

收稿日期:2009-07-27 发布日期:2009-11-16
作者简介:刘晓莉(1970- )，女，博士，副主任医师，主要从事血液病的临床与基础研究。 Email:lammy1102@gmail.com

Human fetal liver cell transplantation in treatment of mucopolysaccharidosis

LIU Xiaoli, WAN Jiangbo, LIANG Hui

Department of Hematology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092， China

Received:2009-07-27 Published:2009-11-16

摘要/Abstract

摘要：

（上海交通大学医学院附属新华医院血液科，上海 200092）摘要：目的探讨用胎肝细胞移植治疗小鼠αL艾杜糖苷酶（IDUA）缺陷引起的粘多糖贮积症（MPS），筛选免疫抑制方案。方法将人胎肝细胞移植给经不同免疫抑制剂方案处理的IDUA缺陷小鼠，流式细胞仪检测移植前、后受体小鼠T细胞亚群（CD3、CD4/CD8比例）；酶联免疫吸附剂测定(ELISA)法检测免疫球蛋白G(IgG)、免疫球蛋白M（IgM）、白介素2（IL2）、肿瘤坏死因子α（TNFα）、干扰素γ（IFNγ）水平；荧光分光光度计法检测血清IDUA活性。结果受体移植后血清中反映免疫状态的指标（T细胞亚群、IL2、TNFα、IFNγ）均显著升高（P＜0.05）；血清IDUA活性在移植后第5天显著提高（P＜0.01），后随时间延长，活性随之衰减；经CTX＋CsA＋FTY720＋强的松联合免疫抑制预处理组在移植后IDUA活性维持最持久。结论胎肝细胞移植能提高IDUA活性。由于免疫排斥反应，移植前应进行免疫抑制预处理，以CTX＋CsA＋FTY720＋强的松联合方案免疫抑制效果最佳。

关键词: 胎肝细胞；移植；粘多糖贮积症；免疫抑制剂

Abstract:

ObjectiveTo study the immunological reaction of mice with mucopolysaccharidosis treated by human fetal liver cell transplantation in order to select an immunosuppressive agent. MethodHuman fetal liver cells(FLCs) were transplanted into αLduronidase (IDUA) deficiency mice pretreated with different immunosuppressive agents. T cell subsets（CD3,CD4/CD8）were detected by flowcytometry, while cytokines(IgG,IgM,IL2, TNFα and IFNγ) by EL ISA, and serum IDUA activity by a fluorospectrophotometer at different stages (before and after transplantation). ResultsThe T cell subsets and cytokines in recipients were significantly increased after FLCs transplantation. Five days after transplantation, IDUA activity reached a peak in all groups (P＜0.01), then gradually decreased. The IDUA activity lasted the longest in the group pretreated with cyclophosphamide cyclosporine FTY720 and predinisone. ConclusionIDUA activity can be raised by FLCs transplantation. Due to immunological rejection, the recipient should be given immunosuppressive therapy. Cyclophosphamide cyclosporine FTY720 in combination with predinisone can give the best immunosuppression.

Key words: Fetal liver cells; Transplantation; Mucopolysaccharidosis; Immunosuppressive agent

中图分类号:

R589.9

刘晓莉，万江波，梁辉. 胎肝细胞移植治疗粘多糖贮积症的实验研究[J]. 山东大学学报(医学版), 2009, 47(11): 59-63.

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