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Synovial mesenchymal stem cells accelerate early remodeling of tendon-bone healing
Authors:Young-Jin Ju  Takeshi Muneta  Hideya Yoshimura  Hideyuki Koga  Ichiro Sekiya
Institution:(1) Section of Orthopedic Surgery, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan;(2) Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo, Japan;(3) Section of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113–8519, Japan
Abstract:Tendon-bone healing is important for the successful reconstruction of the anterior cruciate ligament by using the hamstring tendon. Mesenchymal stem cells (MSCs) have attracted much interest because of their self-renewing potential and multipotentiality for possible clinical use. We previously reported that MSCs derived from synovium had a higher proliferation and differentiation potential than the other MSCs that we examined. The purpose of this study was to investigate the effect and mechanism of the implantation of the synovial MSCs on tendon-bone healing in rats. Half of the Achilles’ tendon grafts of rats were inserted into a bone tunnel from the tibial plateau to the tibial tuberosity with a suture-post fixation. The bone tunnel was filled with MSCs labeled with fluorescent marker DiI or without MSCs as the control. The tendon-bone interface was analyzed histologically, and collagen fibers were quantified. At 1 week, the tendon-bone interface was filled with abundant DiI-positive cells, and the proportion of collagen fiber area was significantly higher in the MSC group than in the control group. By 2 weeks, the proportion of oblique collagen fibers, which appeared to be Sharpey’s fibers, was significantly higher in the MSC group than in the control group. At 4 weeks, the interface tissue disappeared, and the implanted tendon appeared to attach to the bone directly in both groups. DiI-labeled cells could no longer be observed. Implantation of synovial MSCs into bone tunnel thus accelerated early remodeling of tendon-bone healing, as shown histologically. This study was supported in part by grants from the Japan Society for the Promotion of Science (19591752) and from the Center of Excellence Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone at Tokyo Medical and Dental University to T.M. and from the Japan Society for the Promotion of Science (18591657) to I.S.
Keywords:Mesenchymal stem cells  Tendon-bone healing  Anterior cruciate ligament reconstruction  Cell therapy  Synovium  Rat (Sprague Dawley)
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