2025 ISAKOS Biennial Congress Paper
Phase III Clinical Trial for Knee Chondral Lesions Repair Using Scaffold-Free, Impurity-Free Tissue-Engineered Construct Generated From Allogenic Synovial Mesenchymal Stem Cells (Golmestrocel)
Kazunori Shimomura, MD, PhD, Prof., Suita, Osaka JAPAN
Atsuya Watanabe, MD, PhD, Chiba, Chiba JAPAN
Tomoyuki Suzuki, MD, PhD, Sapporo, Hokkaido JAPAN
Koichi Nakagawa, Prof., MD, PhD, Sakura, Chiba JAPAN
Junichi Iwasaki, Chiba, Chiba JAPAN
Ayumu Nakashima, MD, PhD, Yamanashi, Yamanashi JAPAN
Norimasa Nakamura, MD, PhD, Osaka, Osaka JAPAN
Osaka University, Suita, Osaka, JAPAN
FDA Status Not Applicable
Summary
The present study demonstrated the efficacy and feasibility of allogenic scaffold-free tissue-engineered construct from synovial MSCs for cartilage repair via a sutureless and simple implantation procedure, showing promising clinical, MRI, arthroscopic, and histological outcomes.
Abstract
Articular cartilage has limited healing capacity, which can lead to high risk for developing osteoarthritis once damaged. We developed a scaffold-free tissue-engineered construct from autologous synovial membrane mesenchymal stem/stromal cells (MSCs) and demonstrated its safety and effectiveness for cartilage repair in a first-in-human clinical trial. In this study, we performed a phase III randomized controlled trial (JRCT ID: jRCT1080223548) to compare our tissue engineering approach with microfracture for cartilage repair, assessing clinical outcomes up to 52 weeks post-implantation.
76 patients with knee chondral lesions (1.0-5.0 cm²) participated. Allogenic synovial MSCs were cultured with impurity-free, serum-free media to create tissue-engineered constructs (international nonproprietary name: golmestrocel) matching the lesion size. Golmestrocels were implanted into chondral defects without suturing and fixation glue (N=37), while the control group underwent microfracture (N=39). The primary outcomes were the change from baseline to 52 weeks in knee injury and osteoarthritis outcome score (KOOS) overall scores and the histological analysis of repair tissue. Secondary outcomes included the morphological quality of repair tissue, assessed with MRI as well as the arthroscopic analysis of repair tissue at 52 weeks.
No significant differences in adverse events were observed between the two groups. KOOS overall scores significantly improved from baseline to 52 weeks postoperatively in both groups. Histology at 52 weeks indicated that the golmestrocel repair tissue closely resembled hyaline cartilage with higher histological scores, although the difference was not significant between the two groups. The MRI and arthroscopic findings in the golmestrocel group showed more secure defect filling and cartilaginous tissue repair with good integration to adjacent host tissue compared to the microfracture group.
These results demonstrated the efficacy and feasibility of allogenic scaffold-free tissue-engineered construct from synovial MSCs for cartilage repair via a sutureless and simple implantation procedure, showing promising clinical, MRI, arthroscopic, and histological outcomes.