Background: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. Purpose: To determine whether implantation of a composite of allogeneic umbilical cord blood–derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. Results: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group (P =.051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group (P =.001); the overall histologic assessment score was also superior in the UCB-MSC-HA group (P =.036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up (P <.05). There were no differences between the groups in adverse events. Conclusion: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. Registration: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).
Bibliographical noteFunding Information:
One or more of the authors has declared the following potential conflict of interest or source of funding: This study was sponsored and funded by Medipost, the manufacturer of Cartistem. Funding was also received from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number HI14C3484). B.J.C. has received research support from Aesculap/B.Braun, Arthrex, and Regentis; educational support from Medwest; consulting fees from Acumed, Anika Therapeutics, Arthrex, Bioventus, Flexion Therapeutics, Geistlich Pharma, Regentis, Smith & Nephew, Vericel, and Zimmer Biomet; speaking fees from Arthrex and Lifenet Health; royalties from Arthrex, DJO, Elsevier, and Operative Techniques in Sports Medicine; other financial or material support from Athletico and JRF Ortho; hospitality payments from GE Healthcare; and honoraria from Vericel; and he has stock/stock options in Bandgrip, Ossio, and Regentis. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
© The Author(s) 2021.
- cartilage restoration
- full-thickness cartilage defect
- mesenchymal stem cells
- umbilical cord blood