Synovial mesenchymal stem cell-augmented meniscal repair for flap tears: A phase III multicenter clinical trial

Current meniscal preservation treatments are limited to specific tear types. The aim of this multicenter study was to determine whether synovial mesenchymal stem cell transplantation after meniscal suturing could improve knee function at week 52 and to evaluate safety and efficacy at week 104.

This multicenter, single-arm study included Cohort 1 (meniscal flap tears) as the primary cohort and Cohort 2 (other tear types) as an exploratory cohort. Eligible participants were adults (≥18 years) who had failed conservative treatment and had symptomatic tears with an expected resection area ≥100 mm². The primary endpoint was a demonstration that the change in the Lysholm knee score from screening to week 52 in Cohort 1 showed a lower limit of the two-sided 95% confidence interval that exceeded a prespecified 22-point threshold. Secondary endpoints included arthroscopic findings, magnetic resonance imaging assessments, Knee Injury and Osteoarthritis Outcome Score and pain assessed by a Numerical Rating Scale, and Kellgren-Lawrence grade. Cultured synovial mesenchymal stem cells were transplanted onto the injury site four to six weeks after suturing.

Fifteen Cohort 1 and 4 Cohort 2 patients completed week 52 follow-up; 14 and 4 completed week 104. The primary endpoint was achieved, with the lower limit of the 95% confidence interval for Lysholm knee score change (48.7) exceeding the prespecified 22-point threshold at week 52 in Cohort 1. Secondary endpoints showed improvements in patient-reported outcomes, with 71.4% arthroscopic improvement, 80.0% MRI improvement, and 60.0% showing no radiographic progression in Cohort 1. Exploratory Cohort 2 showed similar trends. Improvements were sustained at week 104, with no treatment-related adverse events.

The primary and secondary endpoints demonstrated significant and sustained improvement in knee function and meniscal healing. The findings suggest that this approach could be a treatment option for patients who would otherwise require meniscectomy.