中国组织工程研究

中国组织工程研究 ›› 2014, Vol. 18 ›› Issue (45): 7279-7284.doi: 10.3969/j.issn.2095-4344.2014.45.012

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

脐带间充质干细胞移植治疗类风湿性关节炎患者Th1/Th2、Treg的变化

王黎明1，王立华2，李 铭1，白 雯1，钟占强1，石 军1，周建军1，黄士高1，李 娜2，吉海杰2，刘拥军2，吴明远2   

  1. 1解放军323医院，陕西省西安市 710054；2天津和泽干细胞转化再生医学研究中心，天津市 300381
  • 出版日期:2014-11-05 发布日期:2014-11-05
  • 通讯作者: 刘拥军，博士，教授，天津和泽干细胞转化再生医学研究中心，天津市 300381
  • 作者简介:王黎明，山东省淄博市人，汉族，硕士，主要从事血液病学、风湿免疫病、再生医学研究。
  • 基金资助:

    军区医药卫生计划课题(CLZ12GA23)

Variation of Th1/Th2 and Terg in rheumatoid arthritis patients undergoing umbilical cord mesenchymal stem cell transplantation

Wang Li-ming1, Wang Li-hua2, Li Ming1, Bai Wen1, Zhong Zhan-qiang1, Shi Jun1, Zhou Jian-jun1, Huang Shi-gao1, Li Na2, Ji Hai-jie2, Liu Yong-jun2, Wu Ming-yuan2   

  1. 1the 323rd Hospital of PLA, Xi’an 710054, Shaanxi Province, China; 2Heze Stem Cells and Regenerative Medicine Research Center, Tianjin 300381, China
  • Online:2014-11-05 Published:2014-11-05
  • Contact: Liu Yong-jun, M.D., Professor, Heze Stem Cells and Regenerative Medicine Research Center, Tianjin 300381, China
  • About author:Wang Li-ming, Master, the 323rd Hospital of PLA, Xi’an 710054, Shaanxi Province, China
  • Supported by:

    the Military Medical Health Plan, No. CLZ12GA23

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摘要：

背景：类风湿性关节炎是自身免疫性疾病，传统治疗方法很难有效解决患者免疫耐受机制缺失的问题。随着干细胞再生医学的发展，应用干细胞治疗免疫性疾病成为热点。目前国内外对于细胞移植治疗类风湿性关节炎少有报道。

 

目的：探讨脐带间充质干细胞对类风湿性关节炎患者Th1/Th2、Treg变化的影响，为类风湿性关节炎寻找新的治疗方法。

 

方法：180例类风湿性关节炎患者，其中27例为对照组，给予非类固醇抗炎药和抗风湿药，153例为治疗组，静脉输注细胞数为4×107的脐带间充质干细胞40 mL，用药方案与对照组相同，76例患者在第1次细胞治疗的三四个月后接受了2次脐带间充质干细胞治疗。随访治疗后3，6个月进行临床有效性评估(DAS28、HAQ、ACR20)、类风湿因子、抗CCP抗体、T细胞亚群、Th细胞因子检测。部分2次细胞治疗患者随访至8个月检测Treg、T细胞亚群。

 

结果与结论： ①随访3个月时，细胞治疗组DAS28评分、HAQ评分、ACR20较对照组下降明显，差异有非常显著性意义(P < 0.01)。②脐带间充质干细胞治疗3，6个月的DAS28评分、HAQ评分较治疗前明显下降(P < 0.01)，2次治疗较1次治疗继续下降(P < 0.01)。③治疗后3，6个月γ-干扰素水平较治疗前变化不明显，治疗后6个月白细胞介素4水平较治疗前逐渐上升(P < 0.05)。④治疗后3，6个月Treg较治疗前明显上升(P < 0.01)，同时治疗后Treg升高与ACR明显相关，尤其是ACR70百分率(P < 0.05)；治疗后3个月CD4+ Treg比率明显升高(P < 0.05)，6，8个月时与治疗前相比也是升高趋势，但差异无显著性意义(P > 0.05)。⑤治疗后6个月B细胞水平明显下降(P < 0.05)；治疗后3，6个月类风湿因子较治疗前均明显下降(P < 0.05)。⑥治疗后3，6个月抗CCP抗体和白细胞介素17水平变化不大。结果表明类风湿性关节炎患者给予脐带间充质干细胞治疗后Th1/Th2趋于平衡、Treg升高与临床实验指标及症状的缓解直接相关。因此按风湿病指南用药的同时，协同使用脐带间充质干细胞可改善类风湿性关节炎患者免疫网络效应、调整免疫耐受、改善病情。

 

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程


全文链接：

关键词: 干细胞, 移植, 类风湿性关节炎, 脐带间充质干细胞, 治疗, Th1/Th2, Treg

Abstract:

BACKGROUND: Rheumatoid arthritis is an autoimmune disease, and traditional treatment methods are difficult to effectively solve the patient's lack of immune tolerance mechanisms. With the development of stem cells in regenerative medicine, stem cell therapy has become a hot spot in the treatment of autoimmune diseases.

 
Currently, studies on cell transplantation for the treatment of rheumatoid arthritis are rarely reported.
OBJECTIVE: To study the influence of umbilical cord mesenchymal stem cell therapy on the changes of Th1/Th2 and Treg in rheumatoid arthritis patients, thereby seeking new therapies for rheumatoid arthritis.
METHODS: We selected 180 cases of rheumatoid arthritis, including 27 patients as control group undergoing non-steroidal anti-inflammatory drugs and anti-rheumatic drugs and 153 patients as cell treatment group undergoing intravenous infusion of 40 mL umbilical cord mesenchymal stem cells at a density of 4×107. Dosing regimen was same in the two groups. The 76 of 153 patients accepted second cell therapy at 3-4 months after the first cell therapy. After follow-up of 3 and 6 months, clinical effectiveness evaluation (DAS28, HAQ, ACR20), rheumatoid factor, anti-CCP antibodies, T cell subsets, Th cytokine were detected; for patients with second cell therapy, T cell subsets and Treg were detected at 8 months after treatment.
RESULTS AND CONCLUSION: (1) At 3 months after treatment, the DAS28, HAQ and ACR20 scores were significantly lower in the cell treatment group than the control group (P < 0.01). (2) At 3 and 6 months after cell therapy, the DAS28 and HAQ scores were significantly decreased in the cell treatment group (P < 0.01), and these scores were decreased continuously after second cell therapy (P < 0.01). (3) Interferon-γ level in cells did not change obviously at 3-6 months after treatment, but the interleukin-4 level was gradually increased at 6 months after treatment (P < 0.05). (4) The number of Treg cells was significantly increased at 3-6 months after treatment (P < 0.01), which was closely related to ACR, especially ACR70 percentage (P < 0.05); the ratio of CD4+ Treg was increased significantly at 3 months after treatment (P < 0.05), and this increasing trend was also maintained at 6 and 8 months after treatment, but there was no significant difference (P > 0.05). (5) B cell levels were significantly decreased at 6 months after treatment (P > 0.05); the rheumatoid factor value was significantly decreased at 3-6 months after treatment (P < 0.05). (6) There was no change in anti-CCP antibody and interleukin-17 levels at 3-6 months after treatment. These findings indicate that after treatment with umbilical cord mesenchymal stem cells, the Th1/Th2 tends to balance and Treg level is elevated in rheumatoid arthritis patients, which are directly related to clinical trials and symptomatic relief. Therefore, standard rheumatism medication combined with umbilical cord mesenchymal stem cell transplantation can improve immune network effects, adjust the immune tolerance and prevent illness progress in rheumatoid arthritis patients.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程


全文链接：

Key words: arthritis, rheumatoid, umbilical cord, mesenchymal stem cell transplantation, T-Lymphocytes, regulatory, Th1-Th2 balance

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