Abstract
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.
Highlights
Osteoarthritis (OA) is the most common form of arthritis.[1]
This systematic review and meta-analysis found that Mesenchymal stem cells (MSCs) treatment significantly improved knee pain and self-reported physical function in patients with knee OA
We suggest that more high quality RCTs with stratification for rehabilitation are needed to facilitate a foundation of effective MSC therapy and regenerative rehabilitation
Summary
Osteoarthritis (OA) is the most common form of arthritis.[1]. OA results in cartilage degeneration, chronic knee pain, and disability. Mesenchymal stem cells (MSCs) have emerged as a cell type with great potential for cell-based articular cartilage repair in patients with knee OA.[3] Clinical trials that investigate the effects of MSC treatments in patients with knee OA have recently begun emerging,[4] and results of clinical studies are continuously reported.[5,6] Several meta-analyses summarize the effects of MSC treatment in patients with knee OA;[7,8,9,10] these studies contribute to the establishment of effective cell-based therapies for degenerative cartilage disease Some of these systematic reviews included patients with focal cartilage lesions[8,9,10] or focused on pain and physical function as treatment outcomes,[7,9,10] with a large heterogeneity and lack of evaluation of bias risk.[7,8,9] As knee pain would be discordant with articular cartilage status, understanding the effects of MSC treatment against OA joint degeneration and exploring the mechanisms underlying symptom-modifying MSC treatment are important. Weight-bearing might influence the structural outcome in the postoperative phase of autologous chondrocyte implantation in adults with cartilage defects.[17,18] further investigation of the effects of MSC treatment in patients with knee
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