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间充质干细胞治疗膝关节骨关节炎和软骨缺损的再生潜力:系统评价与荟萃分析

Regenerative Potential of Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis and Chondral Defects: A Systematic Review and Meta-analysis.

作者信息

Maheshwer Bhargavi, Polce Evan M, Paul Katlynn, Williams Brady T, Wolfson Theodore S, Yanke Adam, Verma Nikhil N, Cole Brian J, Chahla Jorge

机构信息

Department of Orthopaedic Surgery, Division of Sports Medicine, Rush University, Medical Center, Chicago, Illinois, U.S.A.

Loyola University Chicago, Chicago, Illinois, U.S.A.

出版信息

Arthroscopy. 2021 Jan;37(1):362-378. doi: 10.1016/j.arthro.2020.05.037. Epub 2020 Jun 1.

DOI:10.1016/j.arthro.2020.05.037
PMID:32497658
Abstract

PURPOSE

To perform a systematic review and meta-analysis evaluating the effects of mesenchymal stem cells (MSCs) on cartilage regeneration and patient-reported pain and function.

METHODS

A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using a PRISMA checklist. The Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, PubMed (2008-2019), EMBASE (2008-2019), and MEDLINE (2008-2019) were queried in July 2019 for literature reporting use of stem cells to treat knee osteoarthritis or chondral defects. Data describing administered treatment, subject population, injection type, duration of follow-up, pain and functional outcomes, and radiographic and magnetic resonance imaging findings were extracted. Risk of bias was assessed using the Downs and Black scale. Meta-analyses adjusted for random effects were performed, calculating pooled effect sizes in terms of patient-reported pain and function, cartilage quality, and cartilage volume.

RESULTS

Twenty-five studies with 439 subjects were identified. There was no significant difference in pain improvement between MSC treatment and controls (pooled standardized mean difference [SMD] = 0.23, P = .30). However, MSC treatment was significantly favored for functional improvement (SMD = 0.66, P < .001). There was improvement in cartilage volume after MSC treatment (SMD = 0.84, P < .001). Regarding cartilage quality, meta-analysis resulted in a small, nonsignificant effect size of 0.37 (95%, -0.03 to 0.77, P = .07). There was risk for potential bias among included studies, with 17 (68%) receiving either a grade of "poor" or "fair."

CONCLUSIONS

The pooled SMD from meta-analyses showed statistically significant effects of MSC on self-reported physical function but not self-reported pain. MSCs provided functional benefit only in patients who underwent concomitant surgery. However, this must be interpreted with caution, as there was substantial variability in MSC composition and mode of delivery. MSC treatment provided significant improvement in cartilage volume but not cartilage quality. Preliminary data regarding therapeutic properties of MSC treatment suggest significant heterogeneity in the current literature, and risk of bias is not negligible.

LEVEL OF EVIDENCE

II, Systematic Review and Meta-analysis.

摘要

目的

进行一项系统评价和荟萃分析,评估间充质干细胞(MSC)对软骨再生以及患者报告的疼痛和功能的影响。

方法

根据PRISMA(系统评价和荟萃分析的首选报告项目)指南并使用PRISMA清单进行系统评价。2019年7月检索了Cochrane系统评价数据库、Cochrane对照试验中心注册库、PubMed(2008 - 2019年)、EMBASE(2008 - 2019年)和MEDLINE(2008 - 2019年),以查找报告使用干细胞治疗膝关节骨关节炎或软骨缺损的文献。提取描述所给予治疗、受试者人群、注射类型、随访持续时间、疼痛和功能结局以及放射学和磁共振成像结果的数据。使用Downs和Black量表评估偏倚风险。进行了针对随机效应的荟萃分析,计算了患者报告的疼痛和功能、软骨质量以及软骨体积方面的合并效应量。

结果

共纳入25项研究,涉及439名受试者。MSC治疗与对照组在疼痛改善方面无显著差异(合并标准化均数差[SMD] = 0.23,P = 0.30)。然而,MSC治疗在功能改善方面显著更具优势(SMD = 0.66,P < 0.001)。MSC治疗后软骨体积有所改善(SMD = 0.84,P < 0.001)。关于软骨质量,荟萃分析得出的效应量较小且无统计学意义,为0.37(95%,-0.03至0.77,P = 0.07)。纳入研究存在潜在偏倚风险,17项(68%)研究的偏倚等级为“差”或“一般”。

结论

荟萃分析的合并SMD显示,MSC对自我报告的身体功能有统计学显著影响,但对自我报告的疼痛无影响。MSC仅在接受同期手术的患者中提供功能益处。然而,由于MSC的组成和给药方式存在很大差异,对此必须谨慎解释说明。MSC治疗使软骨体积有显著改善,但对软骨质量无改善。关于MSC治疗的治疗特性的初步数据表明,当前文献存在显著异质性,且偏倚风险不可忽视。

证据级别

II,系统评价和荟萃分析。

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