人源脐带间充质干细胞移植治疗大鼠佐剂骨关节炎的对照研究  

Human umbilical cord-derived mesenchymal stem cells implantation in treatment of rat adjuvant arthritis

作　　者：蒋峰[1] 杨孝兵[1] 张帆[1] 寿旗扬[2] 徐志国 

机构地区：[1]湖州市第三人民医院风湿免疫科,313000 [2]浙江中医药大学动物实验研究中心 [3]协和华东干细胞基因工程有限公司

出　　处：《浙江医学》2016年第9期603-606,610,I0003,共6页Zhejiang Medical Journal

基　　金：湖州市生物医药重大专项计划(2011ZD2007)

摘　　要：目的探讨人源脐带间充质干细胞(hUc—MSCs)治疗大鼠佐剂骨关节炎(OA)的价值。方法将42只大鼠按抽签法分为7组,G组为正常对照组,其余6组进行右后肢膝关节注射0.1%碘乙酸0.1ml造模;A组造模后第6周处死(空白对照);B组造模后第6周注射0.9%氯化钠溶液,第10周处死;C组造模后第6、8周2次注射0.9%氯化钠溶液,第12周处死;D组造模后第6周1次关节腔注射hUc—MSCs,第10周处死;E组造模后第6、8周2次关节腔注射hUc—MSCs,第12周处死;F组造模后第6、8周2次尾静脉注射hUc—MSCs,第12周处死;各组大鼠造模前后和注射后测定关节肿胀度和疼痛评分;处死后取关节组织病理检查。结果 D、E组较B、C组的关节肿胀度均有减小,E组的消肿作用更显著;而F组的消肿作用不明显;D、E组关节疼痛评分较B、C组均有缓解,E组止痛作用更显著;F组的止痛作用与E组相当。Mankin关节软骨病理分级积分结果提示:D组与B组比较无统计学差异;F组低于C组;而E组低于F组。病理检查提示:A组造模后第6周关节组织病理检查类似于OA病理表现,无宿主与移植物的相互排斥反应发生;B组表现类似A组,C组关节病理破坏较B组重;D组滑膜重度增生侵入关节腔,炎症细胞浸润,其病理破坏较A组重,较C组轻,并且软骨染色较浅;E组滑膜增生和炎症较D组轻,软骨染色较D组更浅;F组关节病理表现与E组基本相仿;在饲养、造模、注射、观察的实验过程中,无明显局部或者全身的宿主与移植物相互排斥反应发生,未发现注射部位、关节感染、坏死等不良反应,无意外疾病和死亡发生。结论 2次关节腔注射和尾静脉注射hUc—MSCs均能较好缓解碘乙酸佐剂OA的疼痛,改善滑膜炎症修复软骨等作用,而且2次关节腔注射hUc—MSCs能更明显能消除关节肿胀,减轻滑膜炎症和软骨损害的病理改变;无明显的不良反应发生;hUc—MSCs治疗OA具有良好的有效性和安全性。Objective To investigate the efficacy of human umbilical cord-derived mesenchymal stem cells （hUc-MSCs） implantation in treatment of rat adjuvant arthritis. Methods Forty two rats were randomly divided into 7 groups with 6 animals in each. Acetic acid was injected in right hind joint to induce the arthritis in groups A, B, C, D, E, F;group G served as blank control group. Rats in group A were sacrificed at wk 6 after the model was made （model group）, rats in group B were injected with normal saline at wk 6 and sacrificed at wk 10; rates in group C were injected with normal saline at wk 6, 8 and sacrificed at wk 12; rats in group D were injected with hUc-MSCs in articular cavity at wk 6 and sacrificed at wk 10; rats in group E were injected with hUc-MSCs in articular cavity at wk 6, 8 and sacrificed at wk 12; rats in group F were injected with hUc-MSCs through tail vein at wk 6, 8 and sacrificed at wk 12. The swelling degree and pain degree of rats before and after model made and before and after treatment were evaluated. Pathological examinations in joints were performed after sacrifice. Results Compared with groups B and C, the joint swelling degree of group D and E was reduced and that of group E were significantly reduced while the change of group F was not significant. Compared with groups B and C, the average pain scores of group D and E were reduced and the analgesic effect in group E and F was more significant. The result of the pathological grades of Mankin articular cartilage showed that there was no difference between group D and group B, that of group F was better than group C while that of group E was better than group F. The pathological examination at wk 6 in groups A and B showed the manifestations of osteoarthritis and no graft rejection responses. In group D, the proliferated synovial membrane invading the aricular cavity with infiltration ofinflammatory cells, the pathological damage was more severe than that of group A, but lighter than group C. The synovial proliferation and inflammati

关 键 词：人源脐带间充质干细胞 佐剂 骨关节炎 实验性 移植注射 

分 类 号：R684.3[医药卫生—骨科学]