人脐带血单个核细胞联合人脐带间充质干细胞疗法对乙型肝炎肝硬化患者肝功能、炎症程度及免疫功能的影响  

Effect of combined treatment with human umbilical cord blood mononuclear cells and human umbilical cord mesenchymal stem cells on liver function,inflammation grade,and immune function in patients with hepatitis B cirrhosis

作　　者：韩霞[1] 云升[1] HAN Xia;YUN Sheng(Stem Cell Laboratory,Affiliated Hospital of Inner Mongolia Medical University,Stem Cell Center of Inner Mongolia Medical University,Hohhot 010050,China)

机构地区：[1]内蒙古医科大学附属医院干细胞实验室,内蒙古医科大学干细胞研究中心,呼和浩特010050

出　　处：《临床肝胆病杂志》2021年第8期1822-1828,共7页Journal of Clinical Hepatology

基　　金：内蒙古医科大学科技百万工程联合资助项目(YKD2017KJBW〔LH〕005);内蒙古自治区科技厅资助项目(201802150)。

摘　　要：目的探讨人脐带血单个核细胞(hUCB-MNCs)联合人脐带间充质干细胞(hUC-MSCs)对乙型肝炎相关失代偿期肝硬化患者的肝功能、炎症程度及免疫功能的影响。方法选取2016年11月-2019年6月在内蒙古医科大学附属医院诊治的11例肝硬化患者,所纳入患者第1周输注1次hUCB-MNCs(>18×10^(9)/次),第2、3、4周每周输注1次hUC-MSCs,每次输注1×10^(6)/kg,在治疗结束的第4、8、12周进行复查,对比治疗前后肝功能、血氨、凝血因子、血清细胞因子及淋巴细胞亚群的变化,同时观察记录神经、精神症状的改变。计量资料组间比较采用单因素重复测量方差分析。结果hUCB-MNCs联合hUC-MSCs治疗后的11例患者其精神、神经症状与细胞输注前相比较有所改善;肝功能各项指标及凝血功能基本趋于正常(P值均<0.05);细胞联合输注后的第12周,血氨水平显著下降(P<0.05);炎性细胞因子IL-6、TNFα水平降低(F值分别为49.497、37.071,P值均<0.05);而抗炎细胞因子TGFβ和IL-10水平显著上升(F值分别为35.843、15.918,P值均<0.05);同时CD3^(+)CD8^(+)T淋巴细胞和CD19^(+)B淋巴细胞均降低(F值分别为52.242、89.097,P值均<0.05);免疫调节性T淋巴细胞CD4^(+)CD25^(+)Treg明显升高(F=17.337,P<0.05)。结论hUCB-MNCs联合hUC-MSCs治疗肝硬化,与细胞输注前相比较,可改善肝功能,减少炎性细胞因子产生,减轻肝脏炎症反应以及肝细胞的破坏,升高免疫调节性T淋巴细胞,从而影响其自身免疫功能。Objective To retrospectively investigate the effect of combined treatment with human umbilical cord blood mononuclear cells(hUCB-MNCs)and human umbilical cord mesenchymal stem cells(hUC-MSCs)on liver function,inflammation grade,and immune function in patients with hepatitis B-related decompensated cirrhosis.Methods 11 patients with liver cirrhosis who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from November 2016 to June 2019 were enrolled in this clinical study and were given infusion of hUCB-MNCs(>18×10^(9)/time)once in the first week and infusion of hUC-MSCs(1×10^(6)/kg)once a week in the second,third,and fourth weeks.Reexamination was performed at 4,8,and 12 weeks after treatment to compare the changes in liver function,blood ammonia,blood coagulation factors,serum levels of cytokines,and lymphocyte subsets after treatment,and the changes in neurological and psychiatric symptoms were observed and recorded.A one-way repeated-measures analysis of variance was used for comparison of continuous data between groups.Results After the combined treatment with hUCB-MNCs and hUC-MSCs,all 11 patients achieved certain improvements in psychiatric and neurological symptoms after infusion,and liver function parameters and blood coagulation function basically returned to normal(all P<0.05).At 12 weeks after the combined infusion of cells,blood ammonia level returned to the normal level(P<0.05),and there were significant reductions in the levels of the inflammatory cytokines interleukin-6 and tumor necrosis factor(F=49.497 and 37.071,both P<0.05)and significant increases in the levels of the anti-inflammatory cytokines transforming growth factor-βand interleukin-10(F=35.843 and 15.918,both P<0.05).There were also significant reductions in the percentages of the cytotoxic cells CD3^(+)CD8^(+)T and CD19^(+)B cells(F=52.242 and 89.097,both P<0.05)and a significant increase in the regulatory T cells CD4^(+)CD25^(+)(F=17.337,P<0.05).Conclusion Combined treatment with hUCB-MNCs and hUC-MSCs for

关 键 词：乙型肝炎 肝硬化 胎血 单核细胞 间充质基质细胞 

分 类 号：R512.62[医药卫生—内科学] R575.2[医药卫生—临床医学]