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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。
Objective To investigate the immunosuppressive regimen of mucopolysaccharidosis (MPS) induced by fetal liver cell transplantation in mice deficient in α-L-adonosidase (IDUA). Methods Human fetal liver cells were transplanted into IDUA-deficient mice treated with different immunosuppressive agents. T-cell subsets (CD3, CD4 / CD8) of recipient mice before and after transplantation were detected by flow cytometry. Enzyme-linked immunosorbent assay The activity of immunoglobulin G (IgG), immunoglobulin M (IgM), interleukin-2 (IL-2), tumor necrosis factor-α (TNF- -γ) levels; serum IDUA activity was measured by fluorescence spectrophotometer. Results The index of serum immunoreactivity (T cell subsets, IL-2, TNF-α and IFN-γ) in the serum after transplantation was significantly increased (P <0.05). The serum IDUA activity was significantly higher on the 5th day after transplantation (P <0.01). With the prolongation of time, the activity decreased. The activity of IDUA in CTX + CsA + FTY720 + prednisone combined immunosuppressive preconditioning group was the longest. Conclusion Fetal hepatocyte transplantation can increase IDUA activity. Due to immune rejection, immunosuppressive pretreatment should be performed before transplantation, and CTX + CsA + FTY720 + prednisone combination has the best immunosuppressive effect.