Yohei Harada

Combination therapy with intra-articular injection of mesenchymal stem cells and articulated joint distraction for repair of a chronic osteochondral defect in the rabbit

The present study investigated intra‐articular injection of bone‐marrow‐derived mesenchymal stem cells (MSCs) combined with articulated joint distraction as treatment for osteochondral defects. Large osteochondral defects were created in the weight‐bearing area of the medial femoral condyle in rabbit knees. Four weeks after defect creation, rabbits were divided into six groups: control group, MSC group, distraction group, distraction + MSC group, temporary distraction group, and temporary distraction + MSC group. Groups with MSC received intra‐articular injection of MSCs. Groups with distraction underwent articulated distraction arthroplasty. Groups with temporary distraction discontinued the distraction after 4 weeks. The rabbits were euthanized at 4, 8, and 12 weeks after treatment except temporary distraction groups which were euthanized at only 12 weeks. Histological scores in the distraction + MSC group were significantly better than in the control, MSC group or distraction group at 4 and 8 weeks, but showed no further improvement. At 12 weeks, the temporary distraction + MSC group showed the best results, demonstrating hyaline cartilage repair with regeneration of the osteochondral junction. In conclusion, joint distraction with intra‐articular injection of MSCs promotes early cartilage repair, and compressive loading of the repair tissue after temporary distraction stimulates articular cartilage regeneration.

Role of Mesenchymal Stem Cells Densities When Injected as Suspension in Joints with Osteochondral Defects

Objective The aim of this study was to evaluate an intraarticular injection of different doses of autologous mesenchymal stem cells (MSCs) for improving repair of midterm osteochondral defect. Design At 4 weeks postoperative marrow stimulation model bilaterally (3 mm diameter; 4 mm depth) in the medial femoral condyle, autologous MSCs were injected into knee joint. Twenty-four Japanese rabbits aged 6 months were divided randomly into 4 groups (n = 6 per group): the control group and and MSC groups including 0.125, 1.25, and 6.25 million MSCs. Repaired tissue was assessed macroscopically and histologically at 4 and 12 weeks after intraarticular injection of MSCs. Results At 12 weeks, there was no repair tissue in the control group. The gross appearance of the 1.25 and 6.25 million MSC groups revealed complete repair of the defect with white to pink tissue at 12 weeks. An osteochondral repair was histologically significantly better in the 1.25 and 6.25 million MSC groups than in the control and 0.125 million MSC groups at 4 and 12 weeks, due to presence of hyaline-like tissue in the deep layer at 4 weeks, and at 12 weeks hyaline cartilage formation at the periphery and fibrous tissue containing some chondrocytes in the deep layer of the center of the defect. Subchondral bone was restructured in the 1.25 and 6.25 million MSC groups, although it did not resemble the normal bone. Conclusion An intraarticular injection of 1.25 or 6.25 million MSCs could promote the repair of subchondral bone, even in the case of midterm osteochondral defect.

Monitoring immune response after allogeneic transplantation of mesenchymal stem cells for osteochondral repair.

The aim of this study was to investigate the safety of using allogeneic magnetically labelled mesenchymal stem cells (m‐MSCs) to ameliorate osteochondral repair, with immune surveillance using a mixed lymphocyte reaction (MLR) assay. Twenty knees of Japanese white rabbits were randomly divided into two groups: the control (autologous) group, where 2 × 105 autologous m‐MSCs were transplanted into the defect site; the experimental (allogeneic) group, where 2 × 105 m‐MSCs from Dutch rabbits were transplanted into the defect of Japanese white rabbits. The rabbits were then euthanized after 12 weeks. The repaired tissue was stained with toluidine blue stain in order to produce histological scoring on the Fortier scale. Splenocytes were used to evaluate anti‐donor alloreactivity by a MLR assay using the carboxyfluorescein diacetate succimidyl ester (CFSE) labelling technique (CFSE‐MLR). In both groups, complete repair of the subchondral bone covered by a layer of chondrogenic tissue was confirmed. Also, there was no histologically significant difference on the Fortier scale. Using the CFSE‐MLR assay, CD4+ T‐cells showed alloreactivity in each combination, while the stimulation index of CD4+ T‐cells was not statistically different between the control and experimental groups. Allogeneic m‐MSCs are a safe alternative source to autologous m‐MSCs, upholding repair of an osteochondral defect for clinical application using universal donor MSCs through a one‐stage surgical procedure. Copyright

Bone mineralization changes of the glenoid in shoulders with symptomatic rotator cuff tear

PurposeComputed tomography osteoabsorptiometry (CTO) is a method to analyze the stress distribution in joints by measuring the subchondral bone density. The purpose of this study was to evaluate the bone mineralization changes of the glenoid in shoulders with rotator cuff tears by CTO and to evaluate whether rotator cuff tears are associated with stress changes in the glenoid.MethodsIn total, 32 patients, who were diagnosed with unilateral rotator cuff tears and underwent arthroscopic rotator cuff repair, were enrolled in this study. They underwent CT scanning of both shoulders pre-operatively and the glenoid was evaluated using CTO. Hounsfield units (HU) in seven areas of the glenoid were compared between the affected and unaffected sides.ResultsThe central area of the glenoid on the affected side had significantly lower HU than on the unaffected side among all patients. Focusing on the rotator cuff tear size and the subscapularis tendon, only patients with larger cuff tears or with subscapularis tendon tears showed significantly lower HU in the central area of the affected side.ConclusionsThis study showed a decrease in bone mineralization density in the central glenoid in shoulders with rotator cuff tear. This change was observed in the case of larger cuff tears and subscapularis tendon tears. Our results help clarify the changes in stress distribution in the shoulder joint caused by symptomatic rotator cuff tears.