口腔生物医学 ›› 2021, Vol. 12 ›› Issue (4): 236-241.

• 论著 • 上一篇    下一篇

人脐带间充质干细胞微囊泡治疗类风湿性关节炎的研究

石媛媛,杨建花,王文哲,李蓓,何小宁   

  1. 空军军医大学第三附属医院组织工程中心
  • 收稿日期:2021-10-13 修回日期:2021-12-10 出版日期:2021-12-25 发布日期:2022-01-04
  • 通讯作者: 何小宁 E-mail:hxn_800222@163.com

Human umbilical cord mesenchymal cells in the treatment of rheumatoid arthritis

  • Received:2021-10-13 Revised:2021-12-10 Online:2021-12-25 Published:2022-01-04

摘要: 目的:探究人脐带间充质干细胞(hUC-MSCs)微囊泡(MVs)对类风湿性关节炎(RA)的治疗。方法:分离、培养人脐带间充质干细胞的微囊泡(hUC-MSCs-MVs),建立胶原诱导型关节炎(CIA)DBA/1J小鼠模型,MVs治疗组鼠尾静脉注射MVs,对照组注射等量PBS。HE染色评估关节炎指数和滑膜病理变化,ELISA检测血清炎性因子的表达。体外培养小鼠骨髓巨噬细胞(BMMD),脂多糖(LPS)处理24 h诱导其向促炎型巨噬细胞分化;MVs再处理24 h后,收集细胞上清,ELISA检测炎性因子表达情况,流式细胞术检测促炎型巨噬细胞表面标志物CD80和CD86表达。结果:经过MVs治疗后,MVs治疗组小鼠的关节炎评分下降(P<0.05),白细胞介素(IL)-1β、IL-6及肿瘤坏死因子α(TNF-α)炎性因子表达下调(P<0.01),HE染色观察到小鼠踝关节炎症得到缓解。hUC-MSCs-MVs有效降低了LPS诱导的BMMD炎性因子及CD80和CD86的表达水平(P<0.05)。结论:hUC-MSCs来源的MVs可以有效缓解CIA小鼠类风湿关节炎症状。

关键词: 类风湿性关节炎, 人脐带间充质干细胞, 微囊泡, 巨噬细胞

Abstract: Objective:To investigate the therapeutic effect of microvesicles (MVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) on rheumatoid arthritis (RA). Methods:In this experiment, microvesicles of human umbilical cord mesenchymal stem cells (hUC-MSCs-MVs) were isolated and constructed to establish the bovine type II collagen induced rheumatoid arthritis (CIA) with DBA/1J mice, which MVs were injected into tail vein of mice, and controls were inject the same volume of PBS. Four weeks later, HE staining was used to assess arthritis index and synovial pathological changes, and the expression of inflammatory factors was detected by ELISA. Bone marrow bone marrow derived macrophage (BMDM) were isolated and treated with LPS for 24 h to induce into pro-inflammatory macrophages. After 24 h of treatment with MVs, the cell supernatant was collected to detect the expression of inflammatory factors by ELISA, and the expression of surface markers CD80 and CD86 of pro-inflammatory macrophages was measure by flow cytometer. Results:The results suggested that the arthritis score of the MVs group was decreased (P<0.05). After MVs treatment in vivo, the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) were down-regulated (P<0.01). HE staining showed that the inflammation of ankle joint was alleviated. The results demonstrated that hUC-MSCs-MVs effectively reduced the expression of inflammatory factors and the expression levels of CD80 and CD86 in macrophage stimulated by LPS (P<0.05). Conclusions:hUC-MSCs-MVs can effectively relieve the symptoms of rheumatoid arthritis in CIA mice.