Intra-articular Injection of Culture-Expanded Mesenchymal Stem Cells Without Adjuvant Surgery in Knee Osteoarthritis: A Systematic Review and Meta-analysis

Abstract

Background: Although many clinical studies have assessed the efficacy of mesenchymal stem cells (MSCs) in knee osteoarthritis, evidence on their efficacy remains unclear owing to heterogeneity of cell entity and concomitant procedures. Purpose: To determine the efficacy of culture-expanded MSCs in knee osteoarthritis in terms of clinical outcome and cartilage repair via meta-analysis of randomized controlled trials (RCTs) without adjuvant surgery. Study Design: Meta-analysis. Methods: PubMed, Embase, the Cochrane Library, CINAHL, and Scopus were searched from inception to December 31, 2018. RCTs with culture-expanded MSCs for treating knee osteoarthritis were included. Studies with adjuvant surgery or cell concentrate were excluded. Quality was assessed by the Cochrane Collaboration risk-of-bias tool. For meta-analysis, data on clinical outcomes were measured using a visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and data on cartilage repair were measured using the Whole-Organ Magnetic Resonance Imaging Score (WORMS); categorization related to improvement was extracted. Results: Six RCTs (203 patients) were included. Two studies were deemed to have a low risk of bias. In pooled analysis, the only significant difference was in the VAS score (mean difference, –13.55; 95% CI, –22.19 to −4.9). In cumulative pain analysis with VAS and WOMAC pain scores, there was significant improvement after treatment (standardized mean difference, –0.54; 95% CI, –0.85 to −0.23). There was no significant difference in cartilage repair assessed by magnetic resonance imaging (standardized mean difference, 0.11; 95% CI, –0.51 to 0.73), WORMS (standardized mean difference, 1.68; 95% CI −14.84 to 18.21), or categorical results (odds ratio, 1.56; 95% CI, 0.32-7.59). Conclusion: Intra-articular injection of culture-expanded MSCs without adjuvant surgery can improve pain for patients experiencing knee osteoarthritis at short-term follow-up (6-12 months). However, evidence regarding function and cartilage repair remains limited.

Efficacy and safety of intra-articular injection of mesenchymal stem cells in the treatment of knee osteoarthritis

“…Our meta-analysis yielded several new findings. At short-term follow-up (6–12 months), patients treated with MSCs had significantly lower VAS scores ( P < .00001) and had a new, smaller range of confidence intervals than previous study by Kim et al, [ 27 ] suggesting a new and more reliable outcome. Second, the total WOMAC score and various subscale scores (pain, stiffness, and function) of patients treated with MSCs were also significantly lower than those of patients in the control group (all P values were less than .05).…”

“…[ 22 – 26 ] From this point of view, the above treatments are only to control symptoms, not to change or delay the progression of the disease. [ 8 , 22 , 27 , 28 ]…”

Mesenchymal stem cells - a promising strategy for treating knee osteoarthritis

“… 27 , 29 Considering that both groups used hyaluronic acid, we believe that the difference in clinical results between the two groups can be considered the effect of MSCs. 44 In addition, MSCs in combination with PRP, stents, growth factors, and even gene therapy also need to be explored to achieve optimal results.…”

Exosomes: roles and therapeutic potential in osteoarthritis

“…Stem cells such as bone marrow mesenchymal stem cells (BMSCs) and adipose mesenchymal stem cells (AMSCs) have shown potent cartilage regeneration ability and have been clinically tested for OA treatment. [158][159][160] Clinical trials of intra-articular injection of MSCs into the knee with OA have exhibited reliable safety and feasibility, 161,162 while this approach could ameliorate the knee society clinical rating system (KSS) and OA outcome score 163,164 and partially alleviate knee pain. [165][166][167][168] However, the detailed mechanisms for this and other stem cell-based OA treatments have not been well clarified.…”