Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immuno...Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.展开更多
目的对比观察环磷酰胺、他克莫司分别与糖皮质激素联合应用治疗特发性膜性肾病的疗效及安全性。方法经肾活检确诊的特发性膜性肾病患者65例,其中采用糖皮质激素联合环磷酰胺(750 mg/m2体表面积)治疗者35例(甲组),采用糖皮质激素联合他...目的对比观察环磷酰胺、他克莫司分别与糖皮质激素联合应用治疗特发性膜性肾病的疗效及安全性。方法经肾活检确诊的特发性膜性肾病患者65例,其中采用糖皮质激素联合环磷酰胺(750 mg/m2体表面积)治疗者35例(甲组),采用糖皮质激素联合他克莫司(靶血药浓度4~8 ng/mL)治疗者30例(乙组)。对比两组治疗3、6、12及18个月时的疾病缓解率,比较治疗前、治疗3、6、12、18个月时的24 h尿蛋白(24 h Upro)、血清白蛋白(ALB)、血肌酐(sCr)、肾小球滤过率(eGFR)、血糖(GLU)、总胆固醇(TC)、甘油三酯(TG),并比较不良反应发生情况。结果甲组治疗6、12、18个月的总缓解率高于治疗3个月时,治疗18个月时的总缓解率高于治疗6个月时;乙组治疗12、18个月的总缓解率高于治疗3个月时(P均<0.05);乙组治疗3、6个月的疾病总缓解率均高于甲组(P均<0.05)。血清24 h Upro、ALB、TC、TG在组间、时间及交互方面差异均有统计学意义(P均<0.05);与治疗前比较,两组治疗3、6、12及18个月的24 h Upro、TC、TG水平低,ALB水平均高(P均<0.05);与治疗3个月时比较,两组治疗6、12及18个月的24 h Upro、TC、TG水平均低,ALB水平高,(P均<0.05);与治疗6个月时比较,甲组治疗12、18个月时的24 h Upro、TC、TG水平低,ALB水平高(P均<0.05),乙组治疗18个月的24 h Upro、TC、TG水平低,ALB水平高(P均<0.05);与甲组相比,乙组治疗3、6个月的24 h Upro、TC、TG水平均低,ALB水平高(P均<0.05)。乙组总不良反应发生率低于甲组(P均<0.05)。结论在糖皮质激素(泼尼松)治疗的基础上,环磷酰胺或他克莫司治疗特发性膜性肾病长期临床效果接近,但他克莫司起效更快,在短期疗程内的疾病缓解率及对24 h Upro、ALB、TC、TG水平改善情况均优于环磷酰胺。他克莫司安全性高于环磷酰胺。展开更多
文摘Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.
文摘目的对比观察环磷酰胺、他克莫司分别与糖皮质激素联合应用治疗特发性膜性肾病的疗效及安全性。方法经肾活检确诊的特发性膜性肾病患者65例,其中采用糖皮质激素联合环磷酰胺(750 mg/m2体表面积)治疗者35例(甲组),采用糖皮质激素联合他克莫司(靶血药浓度4~8 ng/mL)治疗者30例(乙组)。对比两组治疗3、6、12及18个月时的疾病缓解率,比较治疗前、治疗3、6、12、18个月时的24 h尿蛋白(24 h Upro)、血清白蛋白(ALB)、血肌酐(sCr)、肾小球滤过率(eGFR)、血糖(GLU)、总胆固醇(TC)、甘油三酯(TG),并比较不良反应发生情况。结果甲组治疗6、12、18个月的总缓解率高于治疗3个月时,治疗18个月时的总缓解率高于治疗6个月时;乙组治疗12、18个月的总缓解率高于治疗3个月时(P均<0.05);乙组治疗3、6个月的疾病总缓解率均高于甲组(P均<0.05)。血清24 h Upro、ALB、TC、TG在组间、时间及交互方面差异均有统计学意义(P均<0.05);与治疗前比较,两组治疗3、6、12及18个月的24 h Upro、TC、TG水平低,ALB水平均高(P均<0.05);与治疗3个月时比较,两组治疗6、12及18个月的24 h Upro、TC、TG水平均低,ALB水平高,(P均<0.05);与治疗6个月时比较,甲组治疗12、18个月时的24 h Upro、TC、TG水平低,ALB水平高(P均<0.05),乙组治疗18个月的24 h Upro、TC、TG水平低,ALB水平高(P均<0.05);与甲组相比,乙组治疗3、6个月的24 h Upro、TC、TG水平均低,ALB水平高(P均<0.05)。乙组总不良反应发生率低于甲组(P均<0.05)。结论在糖皮质激素(泼尼松)治疗的基础上,环磷酰胺或他克莫司治疗特发性膜性肾病长期临床效果接近,但他克莫司起效更快,在短期疗程内的疾病缓解率及对24 h Upro、ALB、TC、TG水平改善情况均优于环磷酰胺。他克莫司安全性高于环磷酰胺。
