Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, People's Republic of China.
Medical Imaging Center, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangdong, People's Republic of China.
Arthroscopy. 2021 Jan;37(1):340-358. doi: 10.1016/j.arthro.2020.10.016. Epub 2020 Oct 21.
To evaluate the efficacy and safety of intra-articular mesenchymal stromal cells (MSCs) injections for knee osteoarthritis (OA) treatment.
We performed a systematic literature search in PubMed, Embase, Scopus, and the Cochrane Library through April 2020 to identify level I randomized controlled trials (RCTs) that evaluated the clinical efficacy of MSCs versus control treatments for knee OA. Outcomes were analyzed on an intention-to-treat basis with random-effects models.
A total of 13 RCTs were included in the meta-analysis. Compared with placebo, there was no significant difference in VAS for pain (mean difference [MD] 1.62, 95% confidence interval [CI -0.60 to 3.85), WOMAC pain score (MD 1.88, 95% CI -0.21 to 3.98), WOMAC function score (MD -0.67, 95% CI -6.54 to 5.19), or WOMAC stiffness score (MD 0.64, 95% CI -0.86 to 2.14) for MSCs. Moreover, the smallest treatment effect of VAS for pain, WOMAC pain score, WOMAC function score, and WOMAC stiffness score did not exceed the minimum clinically important difference (MCID). Additionally, there was no significant difference in percentage of patients crossing the MCID threshold between MSC and placebo groups for VAS for pain (relative risk [RR] 0.93, 95% CI 0.55 to 1.57) or WOMAC total score (RR 0.40, 95% CI 0.13 to 1.21). Compared with hyaluronic acid (HA), MSC injection was associated with significantly better improvement in VAS for pain (MD 2.00, 95% CI 0.94 to 3.07), WOMAC pain score (MD 4.58, 95% CI 0.49 to 8.67), WOMAC total score (MD 14.86, 95% CI 10.59 to 19.13), and WOMAC stiffness score (MD 1.85, 95% CI 0.02 to 3.69). However, the smallest treatment effect of VAS for pain, WOMAC pain score, WOMAC function score, and WOMAC stiffness score did not exceed the MCID. Moreover, there was no significant difference in percentage of patients crossing the MCID threshold between MSC and HA groups for WOMAC total score (RR 0.57, 95% CI 0.21 to 1.55). We also found that MSCs did not increase adverse events compared with HA and placebo.
Intra-articular MSC injection was not found to be superior to placebo in pain relief and functional improvement for patients with symptomatic knee OA. However, additional direct testing and combination trials of different type of cells, doses, and number of injections of MSCs are required to further enhance clinical decision making for people with symptomatic knee OA.
I, meta-analysis of level I studies.
评估关节内间充质基质细胞（MSCs）注射治疗膝骨关节炎（OA）的疗效和安全性。
我们系统地检索了 PubMed、Embase、Scopus 和 Cochrane 图书馆截至 2020 年 4 月的 I 级随机对照试验（RCT），以评估 MSCs 与对照治疗膝 OA 的临床疗效。采用随机效应模型对意向治疗进行分析。
共有 13 项 RCT 纳入荟萃分析。与安慰剂相比，MSCs 治疗在疼痛视觉模拟评分（VAS）（平均差异 [MD] 1.62，95%置信区间 [CI] -0.60 至 3.85）、WOMAC 疼痛评分（MD 1.88，95% CI -0.21 至 3.98）、WOMAC 功能评分（MD -0.67，95% CI -6.54 至 5.19）和 WOMAC 僵硬评分（MD 0.64，95% CI -0.86 至 2.14）方面无显著差异。此外，疼痛 VAS、WOMAC 疼痛评分、WOMAC 功能评分和 WOMAC 僵硬评分的最小治疗效果均未超过最小临床重要差异（MCID）。此外，在疼痛 VAS （相对风险 [RR] 0.93，95% CI 0.55 至 1.57）或 WOMAC 总评分（RR 0.40，95% CI 0.13 至 1.21）方面，MSC 组与安慰剂组越过 MCID 阈值的患者百分比无显著差异。与透明质酸（HA）相比，MSC 注射在疼痛 VAS（MD 2.00，95% CI 0.94 至 3.07）、WOMAC 疼痛评分（MD 4.58，95% CI 0.49 至 8.67）、WOMAC 总评分（MD 14.86，95% CI 10.59 至 19.13）和 WOMAC 僵硬评分（MD 1.85，95% CI 0.02 至 3.69）方面有显著改善。然而，疼痛 VAS、WOMAC 疼痛评分、WOMAC 功能评分和 WOMAC 僵硬评分的最小治疗效果均未超过 MCID。此外，在 WOMAC 总评分方面，MSC 组与 HA 组越过 MCID 阈值的患者百分比无显著差异（RR 0.57，95% CI 0.21 至 1.55）。我们还发现，与 HA 和安慰剂相比，MSC 并未增加不良反应。
关节内注射 MSC 并未发现比安慰剂在缓解疼痛和改善有症状的膝骨关节炎患者的功能方面更有效。然而，需要进一步进行直接试验和不同类型细胞、剂量和注射次数的联合试验，以进一步增强对有症状的膝骨关节炎患者的临床决策。
I，I 级研究的荟萃分析。
