title: Repetitive allogeneic intraarticular injections of synovial mesenchymal stem cells promote meniscus regeneration in a porcine massive meniscus defect model.
abstract: OBJECTIVE
  A new strategy is required in order to regenerate a meniscus for extensive defects. Synovial mesenchymal stem cells (MSCs) are an attractive cell source for meniscus regeneration due to their high proliferation and chondrogenic potential. We examined the effect of repetitive intraarticular injections of synovial MSCs on meniscus regeneration in a massive meniscal defect of pigs. We followed up the efficacy using MRI evaluation in addition to macroscopic and histological observations.
  
  
  METHODS
  Two weeks before the injection of synovial MSCs, the anterior half of the medial menisci was resected in both knees of pigs. Fifty million allogeneic synovial MSCs were injected into the right knee at 0, 2, and 4 weeks and followed up by sequential MRI. The regenerated meniscus, adjacent articular cartilage, and subchondral bone were evaluated by MRI at 2, 4, 8, 12 and 16 weeks. They were also evaluated macroscopically and histologically at 16 weeks (n = 7).
  
  
  RESULTS
  The resected meniscus regenerated significantly better in the MSC group than in the control group based on histological and MRI analyses. Macroscopically, the meniscal defect already appeared to be filled with synovial tissue at 2 weeks. Articular cartilage and subchondral bone at the medial femoral condyle were also significantly more preserved in the MSC group based on MRI, macroscopic, and histological analyses.
  
  
  CONCLUSIONS
  Intraarticular injections of allogeneic synovial MSCs appeared to promote meniscus regeneration and provide protection at the medial femoral articular cartilage in a porcine massive meniscal defect model.
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Hatsushika
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Muneta
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Horie
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Koga
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Department of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
authors.affiliation: Center for Development of Advanced Medical Technology, Jichi Medical University, Tochigi, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Hishikawa
authors.affiliation: Center for Development of Advanced Medical Technology, Jichi Medical University, Tochigi, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: sekiya.arm@tmd.ac.jp.
authors.forename: I
authors.initials: I
authors.lastname: Sekiya
mesh_terms: D064591:Allografts; D000818:Animals; D002358:Cartilage, Articular / Q000473:pathology; D007270:Injections, Intra-Articular; D007718:Knee Injuries / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008592:Menisci, Tibial / Q000502:physiology* / Q000601:surgery; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D023421:Models, Animal; D012038:Regeneration / Q000502:physiology*; D013552:Swine; D013583:Synovial Membrane / Q000473:pathology; D000070600:Tibial Meniscus Injuries; D016896:Treatment Outcome
keywords: Meniscus; Mesenchymal stem cells; Osteoarthritis; Pig; Regeneration; Synovium