Allogeneic umbilical cord blood-derived mesenchymal stem cells versus microfracture for large full-thickness cartilage defects

Abstract

Background & Aim Currently available treatment options for cartilage restoration are generally applicable to localized, unipolar defects in relatively young patients rather than large, full-thickness lesions in elderly patients. A randomized controlled phase 3 clinical trial was conducted to determine whether implantation of umbilical cord blood-derived MSCs (UCB-MSCs) combined with 4% HA results in reliable cartilage restoration in patients with symptomatic, large full-thickness cartilage defects. In addition, and 5-year extended follow-up observation study was conducted to investigate whether any clinical improvements by this method can be maintained up to 5-years. Methods, Results & Conclusion Methods A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the populations were followed by an observational extended follow-up study of 5 years. Patients with symptomatic, large full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade IV) of knee joint were enrolled in the clinical trial. In case of multiple lesion, the most symptomatic lesion was determined and treated with UCB-MSCs-HA or microfracture. Primary outcome was proportion of subjects improved by ≥1 ICRS grade at 48 weeks according to ICRS Macroscopic Cartilage Repair Assessment. Secondary outcomes included histologic assessment, visual analogue scale pain, WOMAC, IKDC scores, and adverse events. Results Among 114 randomized participants (age 55.9 years), 89 completed the phase 3 clinical trial. Among them 73 were enrolled in the 5-year observational extended follow-up study. Mean defect size was 4.9 (UCB-MSCs-HA group) and 4.0 cm2 (microfracture group) (p=0.051). At 48 week, improvement by ≥1 ICRS grade was in 97.7% (UCB-MSCs-HA group) versus 71.7% (microfracture group) (p=0.001), and the overall histological assessment was superior with UCB-MSCs-HA (p=0.036). No between-group differences in adverse events were observed. Improvement of pain, WOMAC, and IKDC score from baseline were similar between the groups at 48 weeks, but were significantly better in the UCB-MSCs-HA group at 3-5 year follow-up (p Conclusion UCB-MSCs implantation resulted in cartilage repair tissue in more patients and provided robust improvement of knee pain and function than microfracture in patients with symptomatic large full-thickness cartilage defects. UCB-MSCs could be a desirable regenerative treatment option for patients suffering from large full-thickness cartilage defects.