This systematic review with a meta-analysis aimed to summarize the current evidence of the effectiveness of mesenchymal stem cell (MSC) treatment for knee osteoarthritis (OA) and to examine whether rehabilitation is an effect modifier of the effect estimate of MSC treatment. A literature search yielded 659 studies, of which 35 studies met the inclusion criteria (n = 2385 patients; mean age: 36.0–74.5 years). The meta-analysis results suggested that MSC treatment through intra-articular injection or arthroscopic implantation significantly improved knee pain (standardized mean difference [SMD]: −1.45, 95% confidence interval [CI]: −1.94, −0.96), self-reported physical function (SMD: 1.50, 95% CI: 1.09, 1.92), and cartilage quality (SMD: −1.99; 95% CI: −3.51, −0.47). However, the MSC treatment efficacy on cartilage volume was limited (SMD: 0.49; 95% CI: −0.19, 1.16). Minor adverse events (knee pain or swelling) were reported with a wide-ranging prevalence of 2–60%; however, no severe adverse events occurred. The evidence for these outcomes was “very low” to “low” according to the Grades of Recommendation, Assessment, Development and Evaluation system because of the poor study design, high risk of bias, large heterogeneity, and wide 95% CI of the effects estimate. Performing rehabilitation was significantly associated with better SMD for self-reported physical function (regression coefficient: 0.881, 95% CI: 0.049, 1.712; P = 0.039). We suggest that more high quality randomized controlled trials with consideration of the potential rehabilitation-driven clinical benefit would be needed to facilitate the foundation of effective MSC treatment and regenerative rehabilitation for patients with knee OA.

本系统综述和荟萃分析旨在总结间充质干细胞 (MSC) 治疗膝骨关节炎 (OA) 有效性的当前证据，并检查康复是否是 MSC 治疗效果评估的效果修正剂。文献检索共获得 659 项研究，其中 35 项研究符合纳入标准（n  = 2385 名患者；平均年龄：36.0-74.5 岁）。荟萃分析结果表明，通过关节内注射或关节镜植入进行 MSC 治疗可显着改善膝关节疼痛（标准化平均差 [S​​MD]：-1.45，95% 置信区间 [CI]：-1.94，-0.96），自我报告身体功能（SMD：1.50，95％CI：1.09，1.92）和软骨质量（SMD：-1.99；95％CI：-3.51，-0.47）。然而，MSC 对软骨体积的治疗效果有限（SMD：0.49；95% CI：-0.19，1.16）。据报告，轻微不良事件（膝盖疼痛或肿胀）的发生率高达 2-60%；然而，没有发生严重的不良事件。根据推荐、评估、开发和评估系统的等级，这些结果的证据为“非常低”到“低”，因为研究设计不佳、偏倚风险高、异质性大以及效果的 95% CI 较宽估计。进行康复与自我报告的身体功能更好的 SMD 显着相关（回归系数：0.881，95% CI：0.049，1.712；P  = 0.039）。我们建议需要更多高质量的随机对照试验，考虑潜在的康复驱动的临床益处，以促进膝骨关节炎患者有效的间充质干细胞治疗和再生康复的基础。