脐带间充质干细胞移植治疗狼疮性肾炎的疗效与机制

Therapeutic Effects and Mechanism of Umbilical Cord Derived Mesenchymal Stem Cell Transplantation for Lupus Nephritis

目的观察脐带间充质干细胞(h UC-MSC)移植对狼疮性肾炎患者的临床表现、血清因子变化,探讨其疗效和机制.方法 (1)随机、双盲、平行、安慰剂对照观察12例LN患者,分为治疗组,对照组.2组病人基础治疗相同,治疗组病人在基础治疗上增加h UC-MSC治疗.观察治疗前和治疗后2、6月的临床症状和不良反应;(2)检测治疗前和治疗后2、6月血清中肾损伤标记物(抗C1Q、骨桥蛋白(OPN)),炎症相关的细胞因子(IL-4、IL-6、IL-10、IL-18、INF-γ、TGF-β1)的变化;T细胞亚群(CD3/CD4/CD8)的变化.结果 (1)2组患者症状和体征治疗后2月、6个月均有改善,治疗组缓解例数大于对照组,但2组间,差异无统计学意义(P>0.05);(2)SLIDAI评分:2组间分数治疗6个月前后比较,差异有统计学意义(P<0.05);(3)治疗机制:治疗前、治疗后2月、6月2组INF-γ、IL-4、IL-10、IL-6,IL-18,抗C1q、OPN均有变化,但2组间,差异无统计学(P>0.05).T细胞亚群:CD4+T、CD8+T细胞治疗组、对照组,治疗前、治疗后2月、6月组内比较,差异有统计学意义(P<0.05).而组间比较,差异无统计学意义(P>0.05).结论 (1)脐带间充质干细胞移植治疗狼疮性肾炎2组病人临床症状和实验室检查,均有改善,但目前暂无明显差异;(2)2组间炎症因子及肾损伤因子治疗前后比较变化无统计学差异,Huc-MSC治疗LN的机制需更多的临床数据探索;(3)Huc-MSC是否能够重建T细胞亚群平衡需进一步探索.

Objective To study the clinical effects of umbilical cord derived mesenchymal cell transplant on patients with lupus nephritis, and to elucidate the clinical effects and mechanisms of action. Methods We conducted a random, double blind, contrast control that involved 12 SLE patients （1） control team： standard treatmen （2） hUC-MSC treatment team： weekly intravenous pulse for two weeks. We investigated the clinical symptoms, physical signs and adverse effects before treatment, two months and six months after infusion of hUC-MSC. Data on serum biological markers of renal damage （anti-Clq, Osteopontin （OPN） , cellular inflammatory markers （IL-4, IL-6, II-10, IL-17, IL-18, INF-γ, TGF-β1） as well as flow cytometry measurements of T cell sub groups （CD3, CD4, CD8） were taken at baseline, then again at 2 weeks and 6 weeks post treatment. Results （1）Clinical manifestations and physical signs ： the clinical manifestations and physical signs of patients in two groups were improved 2 and 6 months after treatment, and the cases of remission in treatment team were more than the control team, but there was no statistically significant difference （P〉0.05） （2） SLIDAI score ： there was a statistically significant difference in SLIDAI between the treatment teamand the control team （P〈0.05） . （3） Mechanisms of action： the levels of inflammatory （INF-γ, IL-4, IL-10, IL-6, IL-18） and renal injury markers （anti Clq and osteopontin） at 2 and 6 months after treatment in both groups decreased compared to baseline, but there was no statistically significant difference between two teams （P〉0.05） . （4） T-Lymphocyte Subsets： there were statistically significant differences in CD4＋T and CD8＋T cells between before treatment and 2 and 6 monthsafter treatment in both teams （P〈0.05） , but there was no statistically significant difference between two teams （P〉0.05） Conclusions （1） The clinical symptoms and laboratory examination results of patients in two teams were all improved, but there is no statistically significant difference between two teams. （2） There is no statistically significant difference in the inflammatory cytokines and renal injury markers between before and after treatment in two teams, Huc-MSC for treatment of LN still needs more clinical data. （3） Whether the Huc-MSC could reconstruct the balance of the T cell subgroups still needs further exploration.