Expanded mesenchymal stem cell transplantation following marrow stimulation is more effective than marrow stimulation alone in treatment of knee cartilage defect: A systematic review and meta-analysis

Background: Articular cartilage defect of the knee is a debilitating disease and marrow stimulation techniques (MST) is typically regarded as the first line of treatment for full thickness cartilage lesions. However, the ability of MST to induce the repair of cartilage defects with fibrocartilage is limited, raising concerns about the durability of the repaired tissue. Mesenchymal stem cells (MSCs) provide an alternative means of treating cartilage defects. Expanded MSCs transplantation following MST has achieved great success in animal studies, but relevant clinical results are still lacking. Hypothesis: Expanded MSCs transplantation could be an effective adjunctive therapy following MST for knee cartilage defects. Patients and Methods: PubMed, EMBASE, and the Cochrane Library were systematically searched. This investigation considers articles that compare the effectiveness of expanded MSCs transplantation following MST (MSCs/MST) with that of MST alone for treating knee cartilage defects. Data on postoperative clinical outcomes were extracted. In an attempt to analyze trends over time in studies that report repeated measurements, an all time-points meta-analysis (ATM) was undertaken. Results: Five randomized controlled trials (RCTs) were included in this study. In a pooled analysis, the MSCs/MST group exhibited statistically significantly better postoperative international knee documentation committee subjective knee form (IKDC score) than the MST alone group during two years of follow-up (trend estimate through ATM, 0.27; 95% CI: 0.006 to 0.54). Lysholm scores were similarly favorable to MSCs/MST. The MSCs/MST group also yielded a statistically significantly higher magnetic resonance observation of cartilage repair tissue (MOCART) score at final follow-up (Mean Difference, 16.42; 95% CI: 4.44 to 28.40). No trial has identified serious adverse effects. Discussion: This meta-analysis demonstrate that expanded MSCs transplantation is a safe and effective adjunctive therapy. Further RCTs with long-term follow up and cost effectiveness analysis are needed. Level of Evidence: I, Systematic review and meta-analysis.