title: Not single but periodic injections of synovial mesenchymal stem cells maintain viable cells in knees and inhibit osteoarthritis progression in rats.
abstract: We investigated the effects of single or repetitive intra-articular injections of synovial mesenchymal stem cells (MSCs) on a rat osteoarthritis (OA) model, and elucidated the behaviors and underlying mechanisms of the stem cells after the injection.
  
  
  
  One week after the transection of the anterior cruciate ligament (ACL) of wild type Lewis rats, one million synovial MSCs were injected into the knee joint every week. Cartilage degeneration was evaluated with safranin-o staining after the first injection. To analyze cell kinetics or MSC properties, luciferase, LacZ, and GFP expressing synovial MSCs were used. To confirm the role of MSCs, species-specific microarray and PCR analyses were performed using human synovial MSCs.
  
  
  
  Histological analysis for femoral and tibial cartilage showed that a single injection was ineffective but weekly injections had significant chondroprotective effects for 12 weeks. Histological and flow-cytometric analyses of LacZ and GFP expressing synovial MSCs revealed that injected MSCs migrated mainly into the synovium and most of them retained their undifferentiated MSC properties though the migrated cells rapidly decreased. In vivo imaging analysis revealed that MSCs maintained in knees while weekly injection. Species-specific microarray and PCR analyses showed that the human mRNAs on day 1 for 21 genes increased over 50-fold, and increased the expressions of PRG-4, BMP-2, and BMP-6 genes encoding chondroprotective proteins, and TSG-6 encoding an anti-inflammatory one.
  
  
  
  Not single but periodic injections of synovial MSCs maintained viable cells without losing their MSC properties in knees and inhibited osteoarthritis (OA) progression by secretion of trophic factors.
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan; Department of Orthopaedic Surgery, Yokohama City University, Yokohama, 236-0004, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Ozeki
authors.affiliation: Department of Joint Surgery and Sports Medicine, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8510, 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, 113-8510, 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, 113-8510, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mizuno
authors.affiliation: Department of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tsuji
authors.affiliation: Department of Biochemistry and Biophysics, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Mabuchi
authors.affiliation: Department of Biochemistry and Biophysics, Graduate School, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Akazawa
authors.affiliation: Department of Organ Fabrication, Keio University School of Medicine, Tokyo, 160-8582, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, Tokyo, 157-8535, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Futamura
authors.affiliation: Department of Orthopaedic Surgery, Yokohama City University, Yokohama, 236-0004, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.affiliation: Center for Stem Cell and Regenerative Medicine, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan. Electronic address: sekiya.arm@tmd.ac.jp.
authors.forename: I
authors.initials: I
authors.lastname: Sekiya
mesh_terms: D000818:Animals; D006801:Humans; D007270:Injections, Intra-Articular; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells; D010003:Osteoarthritis; D051381:Rats; D011917:Rats, Inbred Lew; D013583:Synovial Membrane
keywords: Mesenchymal stem cells; Osteoarthritis; Periodic injections; Synovium; Trophic factors