Autologous Synovial Mesenchymal Stem Cell Transplantation Suppresses Inflammation Caused by Synovial Harvesting and Promotes Healing in a Micro Minipig Repaired Meniscus Model.

PURPOSE: Allogeneic synovial mesenchymal stem cells (MSCs) effectively promote meniscus healing in micro minipigs. We investigated the effect of autologous synovial MSC transplantation on meniscus healing in a micro minipig model of meniscus repair showing synovitis after synovial harvesting. MATERIALS AND METHODS: Synovium was harvested from the left knee of the micro minipigs after arthrotomy and used to prepare synovial MSCs. The left medial meniscus in the avascular region was injured, repaired, and transplanted with synovial MSCs. First, synovitis was compared after 6 weeks in knees with and without synovial harvesting. Second, the repaired meniscus was compared for the autologous MSC group and the control group (in which synovium was harvested but MSCs were not transplanted) 4 weeks after transplantation. RESULTS: Synovitis was more severe in knees subjected to synovium harvesting than in knees not subjected to harvesting. Menisci treated with autologous MSCs showed no red granulation at the tear of the meniscus, but menisci not treated with MSCS showed red granulation. Macroscopic scores, inflammatory cell infiltration scores, and matrix scores assessed by toluidine blue staining were all significantly better in the autologous MSC group than in the control group without MSCs (n = 6). CONCLUSION: Autologous synovial MSC transplantation suppressed the inflammation caused by synovial harvesting in micro minipigs and promoted healing of the repaired meniscus.

Synovial mesenchymal stem cells promote the meniscus repair in a novel pig meniscus injury model.

Stem cell therapy has potential for the treatment of degenerative meniscus injuries; however, an optimal animal model has not been established. Basic and clinical research show that synovial mesenchymal stem cells (MSCs) promote meniscus repair. The purposes of this study were to create a novel meniscus injury model in microminipigs and to investigate the effectiveness of synovial MSCs on meniscus healing in this model. The posterior portion of the medial meniscus in microminipigs was punctuated 200 times with a 23G needle. Allogenic synovial MSC suspension was placed on the injury site for 10 min for transplantation. The meniscus was evaluated histologically and via sagittal magnetic resonance imaging (MRI), radial MRI reconstructed in three dimensional, and T2 mapping at 1 and 8 weeks. Proteoglycan content stained with safranin-o disappeared 1 week after treatment in both the MSC and control groups but increased at 8 weeks only in the MSC group. Histological scores at 8 weeks were significantly higher in the MSC group than in the control group (n = 6). At 8 weeks, the T2 values of the MSC group were significantly closer to those of a normal meniscus than were those of the control group. High signal intensity areas of the MRIs and positive areas stained with picrosirius red coincided with meniscal lesions. In conclusion, we created a novel meniscus injury model in microminipigs. Evaluation via histology, MRIs, and polarized microscopy showed that transplantation of synovial MSCs improved meniscus healing.

Two- and three-dimensional optical coherence tomography to differentiate degenerative changes in a rat meniscectomy model.

Optical coherence tomography (OCT) is an attractive tool for evaluating cartilage. We developed an OCT system that reconstructs and analyzes a three-dimensional (3D) OCT image by determining the cartilage surface and cartilage-bone boundary from the image taken with currently available OCT devices. We examined the usefulness of 3D renderings of OCT images. In a rat meniscectomized model, the tibia was harvested after 0, 2, 4, or 8 weeks (n = 6). We scanned 300 slices in the y-plane to cover a 4 × 3 × 6-mm section (x-plane; 10 µm × 400 pixels, y-plane; 10 µm × 300 pixels, z-plane; 12.66 µm × 500 pixels) of the medial tibial cartilage. The cartilage surface line and the cartilage-bone boundary were plotted semi-automatically. Slices from 300 two-dimensional (2D) sequential images were systematically and visually checked and corrected, as necessary. We set a region of interest in the cartilage and quantified the cartilage volume in the 3D image. The Osteoarthritis Research Society International (OARSI) histological score was also obtained. The cartilage volume determined using 3D OCT images was 0.291 ± 0.022 mm3 in the normal, 0.264 ± 0.009 mm3 at 2 weeks, 0.210 ± 0.012 mm3 at 4 weeks, and 0.205 ± 0.011 mm3 at 8 weeks. The cartilage volume significantly decreased at 4 and 8 weeks and was significantly correlated with the OARSI histological score (r = -0.674; P = .002). Although the 3D image information could be obtained from the 2D images, the 3D OCT images provided easier-to-understand information because the 3D reconstructed cartilage provided information about the smoothness of the surface, the area, and depth of the defect at a glance.