人脐带间充质干细胞治疗后失代偿期乙型肝炎肝硬化患者的免疫功能和预后  

Effects of human umbilical cord mesenchymal stem cell therapy on the immune function and prognosis in patients with decompensated liver cirrhosis due to hepatitis B

作　　者：方雪晴[1] 张骏飞[2] 宋海燕[2] 陈照林[2] 董静[2] 潘劲劲 陈曦[2] 刘波[2] 陈从新[2] Fang Xue-qing Zhang Jun-fei Song Hai-yan Chen Zhao-lin Dong Jing Pan Jin-jin Chen Xi Liu Bo Chen Cong-xin(Clinical College of PLA of Anhui Medical University, Hefei 230001, Anhui Province, China Department of Infection, No. 105 Hospital of PLA, Hefei 230001, Anhui Province, China)

机构地区：[1]安徽医科大学附属解放军临床学院,安徽省合肥市230001 [2]解放军第一○五医院感染病科,安徽省合肥市230001

出　　处：《中国组织工程研究》2017年第17期2696-2701,共6页Chinese Journal of Tissue Engineering Research

基　　金：南京军区面上课题(15MS048):miR-132修饰的骨髓间充质干细胞治疗休克肝的研究;解放军第105医院科研课题(2013YG04):促肝细胞生长因子诱导人骨髓间充质干细胞与肝细胞定向分化的表观遗传学研究~~

摘　　要：背景:大量体内外实验显示,间充质干细胞对淋巴细胞等免疫细胞有明显的免疫抑制作用。目的:探讨人脐带间充质干细胞对失代偿期乙型肝炎肝硬化患者免疫功能及预后的影响。方法:将118例失代偿期乙型肝炎肝硬化患者随机分为2组,对照组(n=59)进行内科常规治疗;观察组(n=59)在内科常规治疗的基础上进行人脐带间充质干细胞移植,在入院1周内分2次进行,先经肝固有动脉注射10 mL干细胞悬液,然后经静脉注射10 mL干细胞悬液,细胞总数为(4.0-4.5)×10~8。于治疗前、治疗1,4周后,检测血清白细胞介素6、肿瘤坏死因子α、白细胞介素10、转化生长因子β水平,以及外周血淋巴细胞亚群比例;治疗后12周,检测两组MELD评分、Child-Pugh分级变化;随访观察肝衰竭、并发症及生存情况。结果与结论:(1)观察组治疗后1,4周的血清白细胞介素6、肿瘤坏死因子α水平低于对照组(P<0.05或P<0.001),白细胞介素10、转化生长因子β水平高于对照组(P<0.05或P<0.001);(2)观察组治疗后1周的CD3^+CD4^+T细胞、CD4^+CD25^+Treg细胞比例高于对照组(P<0.001),CD3^+CD8^+T细胞、CD3^-CD19^+B细胞低于对照组(P<0.05或P<0.001);治疗后4周的CD3+T细胞、CD3^+CD4^+T细胞、CD4^+CD25^+Treg细胞比例高于对照组(P<0.05或P<0.001),CD3+CD8+T细胞、CD3^-CD19^+B细胞比例低于对照组(P<0.05或P<0.001);(3)观察组MELD评分、Child-Pugh分级低于对照组(P<0.05);(4)观察组未发生肝衰竭,对照组5例出现肝衰竭;观察组并发症发生率低于对照组(P<0.05);观察组随访52周的累计死亡率低于对照组(P<0.05);(5)结果表明,人脐带间充质干细胞移植可减轻失代偿期乙型肝炎肝硬化的炎症反应,改善肝脏功能,降低肝衰竭发生率和死亡率。BACKGROUND： A large number of experiments in vivo and in vitro have shown that mesenchymal stem cells may obviously inhibit the lymphocytes and other immunocytes.OBJECTIVE： To investigate the effect of human umbilical cord mesenchymal stem cell transplantation on the immune function and prognosis of patients suffering decompensated liver cirrhosisn due to hepatitis B.METHODS： 118 patients with decompensated cirrhosis due to hepatitis B were randomly divided into control group （n=59） and observation group （n=59）. The two groups all received normal medical treatment, and in addition, the observation group also received human umbilical cord mesenchymal stem cell transplantation. （4.0-4.5）×108 stem cells were transplanted twice by intervention via proper hepatic artery （10 mL） and intravenous infusion （10 mL） within 1 week after admission. The levels of serum interleukin-6, tumor necrosis factor-α, interleukin-10, transforming growth factor-β and the percentage of lymphocyte subsets in the peripheral blood were determined in the two groups before and 1, 4 weeks after treatment. The model for end-stage liver disease （MELD） score and Child-Pugh score of 118 patients after treatment for 12 weeks were observed and recorded, and liver failure, complications and survival during follow-up period in the two groups were observed. RESULTS AND CONCLUSION： After treatment for 1 and 4 weeks, the levels of serum interleukin-6 and tumor necrosis factor-α in the observation group were significantly lower than those in the control group （P 〈 0.05 or P 〈0.001）, but the levels of serum interleukin-10 and transforming growth factor-β in the observation group were significantly higher than those in the control group （P 〈 0.05 or P 〈 0.001）. After treatment for 1 week, the percentagesof CD3＋CD4＋T cell and CD4＋CD25＋Treg cells in the observation group were significantly higher than those in the control group （P 〈 0.001）, but the percentages of CD3＋CD8＋ T cells and CD3-CD

关 键 词：干细胞 移植 间充质干细胞 脐带 失代偿期肝硬化 细胞因子 淋巴细胞亚群 预后 

分 类 号：R394.2[医药卫生—医学遗传学]