Shimpei Kondo1, Yusuke Nakagawa1,2, Mitsuru Mizuno2, Kenta Katagiri1, Kunikazu Tsuji3, Shinji Kiuchi4, Hideo Ono4, Takeshi Muneta5, Hideyuki Koga1, Ichiro Sekiya2. 1. Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. 2. Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan. 3. Department of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. 4. Yaesu Clinic, Tokyo, Japan. 5. National Hospital Organization Disaster Medical Center, Tokyo, Japan.
Abstract
BACKGROUND: Previous work has demonstrated that patients with cartilage defects of the knee benefit from arthroscopic transplantation of autologous synovial mesenchymal stem cells (MSCs) in terms of magnetic resonance imaging (MRI), qualitative histologic findings, and Lysholm score. However, the effectiveness was limited by the number of cells obtained, so large-sized defects (>500 mm2) were not investigated. The use of MSC aggregates may enable treatment of larger defects by increasing the number of MSCs adhering to the cartilage defect. PURPOSE: To investigate whether transplantation of aggregates of autologous synovial MSCs with 2-step surgery could promote articular cartilage regeneration in microminipig osteochondral defects. STUDY DESIGN: Controlled laboratory study. METHODS: Synovial MSCs derived from a microminipig were examined for in vitro colony-forming and multidifferentiation abilities. An aggregate of 250,000 synovial MSCs was formed with hanging drop culture, and 16 aggregates (for each defect) were implanted on both osteochondral defects (6 × 6 × 1.5 mm) created in the medial femoral condyle and femoral groove (MSC group). The defects in the contralateral knee were left empty (control group). The knee joints were evaluated at 4 and 12 weeks by macroscopic findings and histology. MRI T1rho mapping images were acquired at 12 weeks. For cell tracking, synovial MSCs were labeled with ferucarbotran before aggregate formation and were observed with MRI at 1 week. RESULTS: Synovial MSCs showed in vitro colony-forming and multidifferentiation abilities. Regenerative cartilage formation was significantly better in the MSC group than in the control group, as indicated by International Cartilage Repair Society score (macro), modified Wakitani score (histology), and T1rho mapping (biochemical MRI) in the medial condyle at 12 weeks. Implanted cells, labeled with ferucarbotran, were observed in the osteochondral defects at 1 week with MRI. No significant difference was noted in the modified Wakitani score at 4 weeks in the medial condyle and at 4 and 12 weeks in the femoral groove. CONCLUSION: Transplantation of autologous synovial MSC aggregates promoted articular cartilage regeneration at the medial femoral condyle at 12 weeks in microminipigs. CLINICAL RELEVANCE: Aggregates of autologous synovial MSCs could expand the indications for cartilage repair with synovial MSCs.
BACKGROUND: Previous work has demonstrated that patients with cartilage defects of the knee benefit from arthroscopic transplantation of autologous synovial mesenchymal stem cells (MSCs) in terms of magnetic resonance imaging (MRI), qualitative histologic findings, and Lysholm score. However, the effectiveness was limited by the number of cells obtained, so large-sized defects (>500 mm2) were not investigated. The use of MSC aggregates may enable treatment of larger defects by increasing the number of MSCs adhering to the cartilage defect. PURPOSE: To investigate whether transplantation of aggregates of autologous synovial MSCs with 2-step surgery could promote articular cartilage regeneration in microminipig osteochondral defects. STUDY DESIGN: Controlled laboratory study. METHODS: Synovial MSCs derived from a microminipig were examined for in vitro colony-forming and multidifferentiation abilities. An aggregate of 250,000 synovial MSCs was formed with hanging drop culture, and 16 aggregates (for each defect) were implanted on both osteochondral defects (6 × 6 × 1.5 mm) created in the medial femoral condyle and femoral groove (MSC group). The defects in the contralateral knee were left empty (control group). The knee joints were evaluated at 4 and 12 weeks by macroscopic findings and histology. MRI T1rho mapping images were acquired at 12 weeks. For cell tracking, synovial MSCs were labeled with ferucarbotran before aggregate formation and were observed with MRI at 1 week. RESULTS: Synovial MSCs showed in vitro colony-forming and multidifferentiation abilities. Regenerative cartilage formation was significantly better in the MSC group than in the control group, as indicated by International Cartilage Repair Society score (macro), modified Wakitani score (histology), and T1rho mapping (biochemical MRI) in the medial condyle at 12 weeks. Implanted cells, labeled with ferucarbotran, were observed in the osteochondral defects at 1 week with MRI. No significant difference was noted in the modified Wakitani score at 4 weeks in the medial condyle and at 4 and 12 weeks in the femoral groove. CONCLUSION: Transplantation of autologous synovial MSC aggregates promoted articular cartilage regeneration at the medial femoral condyle at 12 weeks in microminipigs. CLINICAL RELEVANCE: Aggregates of autologous synovial MSCs could expand the indications for cartilage repair with synovial MSCs.
Authors: Zhenhong Ni; Siru Zhou; Song Li; Liang Kuang; Hangang Chen; Xiaoqing Luo; Junjie Ouyang; Mei He; Xiaolan Du; Lin Chen Journal: Bone Res Date: 2020-06-19 Impact factor: 13.567
Authors: Zhenhong Ni; Siru Zhou; Song Li; Liang Kuang; Hangang Chen; Xiaoqing Luo; Junjie Ouyang; Mei He; Xiaolan Du; Lin Chen Journal: Bone Res Date: 2020-06-19 Impact factor: 13.567
Authors: Timothy P Liu; Pin Ha; Crystal Y Xiao; Sang Yub Kim; Andrew R Jensen; Jeremiah Easley; Qingqiang Yao; Xinli Zhang Journal: Front Cell Dev Biol Date: 2022-09-06