间充质干细胞对克罗恩病合并瘘管疗效的meta分析

胡旻萱; 王玉丰; 李云涛; 季国忠

doi:10.16766/j.cnki.issn.1674-4152.004064

间充质干细胞对克罗恩病合并瘘管疗效的meta分析

doi: 10.16766/j.cnki.issn.1674-4152.004064

1.
南京医科大学第二附属医院全科医学科，江苏南京 210011
2.
南京医科大学第二附属医院消化内科，江苏南京 210011

基金项目:

江苏省卫健委面上项目 M2022045

详细信息

通讯作者:
季国忠，E-mail: jgzzl@163.com

中图分类号: R574
计量
- 文章访问数: 12
- HTML全文浏览量: 10
- PDF下载量: 2
- 被引次数: 0
出版历程
- 收稿日期: 2024-11-18
- 网络出版日期: 2025-09-04

Efficacy of mesenchymal stem cells in the treatment of fistulas in Crohn's disease: a meta-analysis

1.
Department of General Practice, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, China

摘要

摘要: 目的系统评价间充质干细胞对克罗恩病合并瘘管的疗效。方法搜索CNKI、Wanfang、PubMed、Web of Science等数据库，收集自建库至2024年8月29日的相关临床试验，由2位研究者独立评估筛选纳入文献，再采用RevMan 5.4.1及R 4.2.2软件进行meta分析。结果共纳入14篇文献，均为随机对照试验，共891例患者。间充质干细胞所致的瘘管愈合率在短期(P=0.02)、中期(P=0.02)和长期(P=0.04)随访中均高于对照组，二者在远期(P=0.22)疗效中差异无统计学意义。以联合缓解(Z=2.33，P=0.02)或临床缓解(Z=2.19，P=0.03)作为瘘管愈合的评价标准，试验组的愈合率均高于对照组，且亚组间无异质性(I²=0%，P=0.91)。采用脂肪或骨髓来源、自体或异体来源、中等及大剂量的间充质干细胞相较对照组均获得更高的瘘管愈合率。根据瘘管大小注射间充质干细胞的瘘管愈合率高于对照组，单次注射固定剂量瘘管愈合率与对照组比较差异无统计学意义。结论间充质干细胞治疗克罗恩病合并瘘管作为一种有效的新手段，较传统疗法可获得更高的临床缓解率及联合缓解率，未来需要开展更多的随机对照试验进一步研究。
- 克罗恩病 /
- 间充质干细胞 /
- 瘘管愈合率 /
- Meta分析
Abstract: Objective To systematically evaluate the effectiveness of mesenchymal stem cells (MSCs) in the treatment of fistulas in Crohn's disease (CD). Methods We searched CNKI, Wanfang, PubMed, Web of Science and other databases from inception to August 29, 2024. The eligible trials were independently evaluated and screened by two researchers. RevMan 5.4.1 and R 4.2.2 software were used to perform the meta-analysis. Results A total of 14 articles were included in the meta-analysis, all of which were randomized controlled trials (RCTs), encompassing a cumulative sample of 891 patients. results showed that compared with control groups, the fistula healing rate (FHR) induced by MSCs was higher in short-term (P=0.02), medium-term (P=0.02) and long-term (P=0.04) follow-up phases, while there was no statistically significant difference between the two groups in over-long-term (P=0.22). Using combined remission (Z=2.33, P=0.02) or clinical remission (Z=2.19, P=0.03) as the criteria for evaluating FHR, the experimental groups showed a higher FHR compared to the control group. Additionally, no heterogeneity was observed among subgroups (I²=0%, P=0.91). The use of MSCs derived from fat or bone marrow, autologous or allogeneic sources, medium or large doses achieved higher FHR compared to the control group. The FHR of injecting MSCs based on the size of the fistula was higher than that of the control group, while there was no statistically significant difference in the FHR between the two groups when treated in a single injection with a fixed dose. Conclusion The use of MSCs offers an emerging and effective approach for fistulizing CD treatment, which can lead to a higher rate of clinical and combined remission. More RCTs need to be performed in the future.
- Crohn's disease /
- Mesenchymal stem cells /
- Fistula healing rate /
- Meta-analysis

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图 1 文献偏倚风险评估结果

Figure 1. Risk of bias in the included studies

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图 2 MSCs对CD并发瘘管不同随访时间的疗效

注：A为治疗后3个月内；B为治疗后3~6个月；C为治疗后6个月~2年；D为治疗2年后。

Figure 2. Efficacy of MSCs for fistulas in different follow-up phases

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图 3 不同评价标准的疗效比较

Figure 3. Efficacy of MSCs with different evaluation criteria

下载: 全尺寸图片幻灯片

表 1 纳入文献基本信息

Table 1. Basic information of included literatures

临床试验项目	发表地	瘘管类型	MSC来源	MSC类型	实验组注射方式和剂量	研究	联合缓解(试验组vs.对照组)	临床缓解(试验组vs.对照组)	随访时间
1	西班牙	肛周瘘、直肠阴道瘘	自体	脂肪	根据瘘管大小注射：第1次：2×10⁷/mL 第2次：4×10⁷/mL	GARCIA-OLMO D(2009)^[16] GUADALAJARA H(2012)^[17]	2/5 vs. 1/3	5/7 vs. 1/7	8周 38周
2	荷兰	肛周瘘	同种异体	骨髓	各组使用固定剂量注射： 1组：1×10⁷/mL 2组：3×10⁷/mL 3组：9×10⁷/mL	MOLENDIJK I(2015)^[22] BARNHOORN M C(2020)^[14]	3/5;4/5;1/5 vs. 1/6 2/5;4/5;1/5 vs. 2/6 4/5;4/5;1/5 vs. 2/6 3/4;4/4;1/5 vs. 0/3		6周 12周 24周 4年
3	欧洲七国及以色列	肛周瘘	同种异体	脂肪	使用固定剂量注射： 12×10⁷/mL	PANÉS J(2016)^[25] PANÉS J(2018)^[24] GARCIA-OLMO D(2022)^[15] PANÉS J(2022)^[23]	53/103 vs. 36/101 58/103 vs. 39/101	57/103 vs. 43/101 61/103 vs. 42/101 16/25 vs. 7/15 20/25 vs. 7/15 14/25 vs. 6/15 29/43 vs. 24/46 23/43 vs. 20/46 23/43 vs. 21/46	24周 52周 24周 52周 104周 52周 104周 156周
4	中国	肛周瘘	自体	脂肪	根据瘘管大小注射： 5×10⁶/mL	ZHOU C(2020)^[27]	10/11 vs. 5/11 8/11 vs. 6/11 7/11 vs. 6/11		3个月 6个月 1年
5	美国	肛周瘘、直肠阴道瘘、储袋瘘	同种异体	骨髓	根据瘘管大小注射：第1次：7.5×10⁷/mL 第2次：7.5×10⁷/mL	LIGHTNER A L(2023)^[19] LIGHTNER A L(2023)^[20] LIGHTNER A L(2024)^[21] LIGHTNER A L(2024)^[18]	7/18 vs. 2/5 15/18 vs. 2/5 2/14 vs. 0/6 4/13 vs. 1/5 3/15 vs. 0/4 6/12 vs. 0/4 24/46 vs. 3/14 19/37 vs. 1/11	7/18 vs. 2/5 15/18 vs. 2/5 2/14 vs. 0/6 4/13 vs. 1/5 3/15 vs. 0/4 6/12 vs. 0/4 24/46 vs. 3/14 19/37 vs. 2/11	3个月 6个月 3个月 6个月 3个月 6个月 6个月 12个月
6	欧洲七国及以色列	肛周瘘	同种异体	脂肪	使用固定剂量注射： 12×10⁷/mL	SERCLOVA Z(2024)^[26]	138/283 vs. 132/285 116/283 vs. 113/285	141/283 vs. 134/285 122/283 vs. 118/285	24周 52周

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