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北京大学学报（医学版） ›› 2018, Vol. 50 ›› Issue (6): 1014-1021. doi: 10.19723/j.issn.1671-167X.2018.06.013

• 论著 • 上一篇    下一篇

间充质干细胞治疗系统性红斑狼疮有效性的meta分析

刘爽1,郭雨龙2,杨静逸3,王维1,徐健1,△()   

  1. 1. 昆明医科大学第一附属医院风湿免疫科, 昆明 650032
    2. 云南省阜外心血管病医院心血管内科,昆明 650000
    3. 云南舜喜再生医学工程有限公司研究中心, 昆明 650000
  • 收稿日期:2018-07-10 出版日期:2018-12-18 发布日期:2018-12-18
  • 通讯作者: 徐健 E-mail:casxujian@163.com
  • 基金资助:
    国家自然科学基金(81160379);国家自然科学基金(81460256);国家自然科学基金(81560233);国家自然科学基金(81501406);国家自然科学基金(81760296);云南省科技厅-昆明医科大学应用基础研究联合基金(2017FE467);云南省科技厅-昆明医科大学应用基础研究联合基金(2017FE467(-138));云南省医疗卫生单位内设研究机构科研项目(2014NS171);云南省医疗卫生单位内设研究机构科研项目(2016NS026);云南省医疗卫生单位内设研究机构科研项目(2016NS052);云南省医疗卫生单位内设研究机构科研项目(2017NS051);云南省医疗卫生单位内设研究机构科研项目(2018NS0133);云南省医疗卫生单位内设研究机构科研项目(2018NS0134);云南省高层次卫生计生技术后备人才基金(H-2017068);云南省中青年学术技术带头人后备人才基金(2015HB071);昆明医科大学“百名中青年学术和技术骨干”基金(60117190457);昆明医科大学“百名中青年学术和技术骨干”基金(CXTD201613)

Efficacy of mesenchymal stem cells on systemic lupus erythematosus:a meta-analysis

Shuang LIU1,Yu-long GUO2,Jing-yi YANG3,Wei WANG1,Jian XU1,△()   

  1. 1. Department of Rheumatology and Immunology, First Affiliated Hospital of Kunming Medical University, Kunming 650032, China
    2. Department of Cardiology, Yunnan Provincial Fuwai Cardiovascular Disease Hospital, Kunming 650000, China
    3. Yunnan Shunxi Regeneration Medical Engineering Co., Ltd, Kunming 650000, China
  • Received:2018-07-10 Online:2018-12-18 Published:2018-12-18
  • Contact: Jian XU E-mail:casxujian@163.com
  • Supported by:
    Supported by the National Natural Science Foundation of China(81160379);Supported by the National Natural Science Foundation of China(81460256);Supported by the National Natural Science Foundation of China(81560233);Supported by the National Natural Science Foundation of China(81501406);Supported by the National Natural Science Foundation of China(81760296);Yunnan Applied Basic Research Projects-Union Foundation(2017FE467);Yunnan Applied Basic Research Projects-Union Foundation(2017FE467(-138));the Funding of Yunnan Provincial Health Science and Technology Plan(2014NS171);the Funding of Yunnan Provincial Health Science and Technology Plan(2016NS026);the Funding of Yunnan Provincial Health Science and Technology Plan(2016NS052);the Funding of Yunnan Provincial Health Science and Technology Plan(2017NS051);the Funding of Yunnan Provincial Health Science and Technology Plan(2018NS0133);the Funding of Yunnan Provincial Health Science and Technology Plan(2018NS0134);Yunnan Provincial Fund for High Level Reserve Talents in Health Science(H-2017068);Yunnan Provincial Fund for Preparatory Young Leaders in Academic and Technology(2015HB071);Yunnan Provincial Fund for Preparatory Young Leaders in Academic and Technology (2015HB071), the Hundred-Talent Program of Kunming Medical University(60117190457);Innovative Research Team of Kunming Medical University(CXTD201613)

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摘要：

目的: 间充质干细胞(mesenchymal stem cell,MSC)用于治疗难治性系统性红斑狼疮(systemic lupus erythematosus,SLE)和狼疮性肾炎已有10余年的历史,但相关研究多为自身对照研究,随机对照研究(randomized controlled trial,RCT)较少,循证医学证据不足。本研究采用荟萃分析方法系统评价MSC治疗SLE的有效性。方法: 计算机检索PubMed数据库、Cochrane Library数据库、万方数据库、维普全文数据库发表的采用MSC治疗SLE的RCT和自身对照研究,截止日期至2018年6月1日。由2位研究者独立按照纳入与排除标准实施文献筛选和数据收集。以SLE疾病活动评分、24 h尿蛋白定量和补体C3定量为研究终点,应用Revman 5.3软件进行荟萃分析。结果: 共纳入8项研究,共213例患者,其中3项研究为RCT,包含66例患者。分析结果显示,MSC可降低SLE疾病活动评分[标准化均数差(standard mean difference,SMD)=-1.76,95%CI:-2.00~-1.51,P<0.001],可降低蛋白尿水平(SMD=-1.74,95%CI:-2.46~-1.03,P<0.001),改善补体C3水平(SMD=1.28,95%CI:0.93~1.62,P<0.001)。共有4项研究报道了不良事件。结论: MSC可用于治疗难治性SLE和狼疮性肾炎,现有证据表明,其可改善疾病活动程度、蛋白尿和补体水平,确切疗效仍需进一步大规模高质量的RCT证实。

关键词: 间充质干细胞, 系统性红斑狼疮, 狼疮性肾炎, Meta分析

Abstract:

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease with multi-organ involvement and several typical autoantibodies. Mesenchymal stem cells (MSC) are multipotent stem cells with low immunogenicity that can differentiate into various kinds of cells, such as bone, cartilage, fat and skin tissue. MSC have immunomodulatory and reparative properties through interactions with immune cells. MSC have been used in the treatment of refractory SLE and lupus nephritis patients for more than ten years. Most clinical studies were self-controlled studies and only a few were randomized controlled trials. The objective of this study was to use meta-analysis method to evaluate the efficacy and safety of MSC treatment in SLE patients. Methods:The PubMed, Cochrane Library, Wanfang and VIP databases were searched for published randomized controlled trials and self-controlled studies before June 1, 2018. The search terms included the Chinese and English versions of mesenchymal stem cells, Mesenchymal Stromal Cells [Mesh], systemic lupus erythematosus, lupus, Lupus Erythematosus, Systemic [Mesh]. Two authors independently screened the literatures, assessed the quality of the studies and collected data according to the inclusion and exclusion criteria. The endpoints were the SLE disease activity index, 24 h urine protein and complement C3. Meta-analysis was performed with the Revman 5.3 software according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. Results:Eight studies involving 213 patients were included and three of the studies were randomized controlled trials with 66 patients involved. The MSC group showed that the SLE disease activity index decreased significantly [standard mean difference (SMD)=-1.76, 95% confidence interval (CI):-2.00 to -1.51, P<0.001), the 24 h urine protein decreased significantly (SMD=-1.74, 95%CI:-2.46 to -1.03, P<0.001), as well as the complement C3 increased significantly (SMD=1.28, 95%CI: 0.93 to 1.62, P<0.001). Four studies reported adverse events including fever, diarrhea and headache during the infusion. Conclusion:Current evidences showed that MSC could improve the disease activity, proteinuria and hypocomplementemia in SLE patients. Large scale and high-quality randomized controlled trials are required to validate the efficacy and safety of MSC treatment in SLE patients.

Key words: Mesenchymal stem cell, Systemic lupus erythematosus, Lupus nephritis, Meta-analysis

中图分类号: 

  • R593.24

图1

文献筛选流程图"

"

"

表3

自身对照研究的质量评价"

Study Representativeness of the exposed cohort Selection
of the non-
exposed cohort		 Ascertainment of
exposure		 Demonstration that the outcome of
interest was
not present
at baseline		 Comparability of cohorts on the basis of design or analysis Assessment of the out-
come		 Was follow-up enough
for outcomes
to occur?		 Adequacy of
follow-up of
cohorts
Gu, et al, 2014[15] Yes NA Yes Yes NA Yes Yes Yes
Zhu, et al, 2016[17] Yes NA Yes Yes NA Yes No Yes
Li, et al, 2016[13] Yes NA Yes Yes NA Yes Yes Yes
Qiu, et al, 2016[18] Yes NA Yes Yes NA Yes Yes Yes
Bai, et al, 2017[12] Yes NA Yes Yes NA Yes Yes Yes

图2

试验组和对照组的SLEDAI比较"

图3

试验组和对照组的24 h尿蛋白定量比较"

图4

试验组和对照组的补体C3定量比较"

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ISSN 1671-167X
CN 11-4691/R
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