title: Synovial mesenchymal stem cells promote meniscus regeneration augmented by an autologous Achilles tendon graft in a rat partial meniscus defect model.
abstract: Although meniscus defects and degeneration are strongly correlated with the later development of osteoarthritis, the promise of regenerative medicine strategies is to prevent and/or delay the disease's progression. Meniscal reconstruction has been shown in animal models with tendon grafting and transplantation of mesenchymal stem cells (MSCs); however, these procedures have not shown the same efficacy in clinical studies. Here, our aim was to investigate the ability of tendon grafts pretreated with exogenous synovial-derived MSCs to prevent cartilage degeneration in a rat partial meniscus defect model. We removed the anterior half of the medial meniscus and grafted autologous Achilles tendons with or without a 10-minute pretreatment of the tendon with synovial MSCs. The meniscus and surrounding cartilage were evaluated at 2, 4, and 8 weeks (n = 5). Tendon grafts increased meniscus size irrespective of synovial MSCs. Histological scores for regenerated menisci were better in the tendon + MSC group than in the other two groups at 4 and 8 weeks. Both macroscopic and histological scores for articular cartilage were significantly better in the tendon + MSC group at 8 weeks. Implanted synovial MSCs survived around the grafted tendon and native meniscus integration site by cell tracking assays with luciferase+, LacZ+, DiI+, and/or GFP+ synovial MSCs and/or GFP+ tendons. Flow cytometric analysis showed that transplanted synovial MSCs retained their MSC properties at 7 days and host synovial tissue also contained cells with MSC characteristics. Synovial MSCs promoted meniscus regeneration augmented by autologous Achilles tendon grafts and prevented cartilage degeneration in rats.
authors.affiliation: Department of Joint Surgery and Sports medicine.|Department of Orthopaedic Surgery, Yokohama City University, Yokohama, Japan.
authors.forename: Nobutake
authors.initials: N
authors.lastname: Ozeki
authors.affiliation: Department of Joint Surgery and Sports medicine.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Muneta
authors.affiliation: Department of Joint Surgery and Sports medicine.
authors.forename: Seiya
authors.initials: S
authors.lastname: Matsuta
authors.affiliation: Department of Joint Surgery and Sports medicine.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Koga
authors.affiliation: Department of Joint Surgery and Sports medicine.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Cartilage Regeneration, Graduate School of Medicine.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tsuji
authors.affiliation: Department of Biochemistry and Biophysics, Graduate School of Health care Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yo
authors.initials: Y
authors.lastname: Mabuchi
authors.affiliation: Department of Biochemistry and Biophysics, Graduate School of Health care Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Akazawa
authors.affiliation: Department of Organ Fabrication, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Department of Orthopaedic Surgery, Yokohama City University, Yokohama, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Saito
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sekiya
mesh_terms: D000125:Achilles Tendon / Q000166:cytology*; D000818:Animals; D002358:Cartilage, Articular; D002454:Cell Differentiation / Q000502:physiology*; D004195:Disease Models, Animal; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D012038:Regeneration / Q000502:physiology*; D044968:Regenerative Medicine / Q000379:methods; D013583:Synovial Membrane / Q000166:cytology*
keywords: Arthritis; Cellular therapy; Mesenchymal stem cells; Stem cell transplantation