Intra-articular Injected Synovial Stem Cells Differentiate into Meniscal Cells Directly and Promote Meniscal Regeneration Without Mobilization to Distant Organs in Rat Massive Meniscal Defect

Authors

  • Masafumi Horie,

    1. Section of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
    Search for more papers by this author
  • Ichiro Sekiya,

    Corresponding author
    1. Section of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    • Section of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo 113-8519, Japan
    Search for more papers by this author
    • Telephone: +81-3-5803-4675; Fax: +81-3-5803-0266

  • Takeshi Muneta,

    1. Section of Orthopedic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
    2. Global Center of Excellence Program and International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo, Japan
    Search for more papers by this author
  • Shizuko Ichinose,

    1. Instrumental Analysis Research Center, Tokyo Medical and Dental University, Tokyo, Japan
    Search for more papers by this author
  • Kenji Matsumoto,

    1. Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan
    Search for more papers by this author
  • Hirohisa Saito,

    1. Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan
    Search for more papers by this author
  • Takashi Murakami,

    1. Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
    Search for more papers by this author
  • Eiji Kobayashi

    Corresponding author
    1. Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan
    • Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan
    Search for more papers by this author
    • Telephone: +81-285-58-7446; Fax: +81-285-44-5365


  • First published online in STEM CELLSExpress January 8, 2009.

  • Author contributions: M.H.: conception and design, data analysis, collection of data, and manuscript writing; I.S.: conception and design, financial support, manuscript writing, final approval of manuscript; T. Muneta: conception and design, financial support, and administrative support; S.I.: electron microscopy; K.M.: microarray and real-time PCR; H.S.: microarray and real-time PCR; T. Murakami: provision of study material and manuscript writing; E.K.: conception and design, financial support, administrative support, provision of study material, manuscript writing.

Abstract

Osteoarthritis in the knees, which can be caused by meniscal defect, constitutes an increasingly common medical problem. Repair for massive meniscal defect remains a challenge owing to a lack of cell kinetics for the menisci precursors in knee joint. The synovium plays pivotal roles during the natural course of meniscal healing and contains mesenchymal stem cells (MSCs) with high chondrogenic potential. Here, we investigated whether intra-articular injected synovium-MSCs enhanced meniscal regeneration in rat massive meniscal defect. To track the injected cells, we developed transgenic rats expressing dual luciferase (Luc) and LacZ. The cells derived from synovium of the rats demonstrated colony-forming ability and multipotentiality, both characteristics of MSCs. Hierarchical clustering analysis revealed that gene expression of meniscal cells was closer to that of synovium-MSCs than to that of bone marrow-MSCs. Two to 8 weeks after five million Luc/LacZ+ synovium-MSCs were injected into massive meniscectomized knee of wild-type rat, macroscopically, the menisci regenerated much better than it did in the control group. After 12 weeks, the regenerated menisci were LacZ positive, produced type 2 collagen, and showed meniscal features by transmission electron microscopy. In in-vivo luminescence analysis, photons increased in the meniscus-resected knee over a 3-day period, then decreased without detection in all other organs. LacZ gene derived from MSCs could not be detected in other organs except in synovium by real-time PCR. Synovium-MSCs injected into the massive meniscectomized knee adhered to the lesion, differentiated into meniscal cells directly, and promoted meniscal regeneration without mobilization to distant organs. STEM CELLS 2009;27:878–887

Ancillary