Synovial Mesenchymal Stem Cells Promote Meniscus Regeneration Augmented by an Autologous Achilles Tendon Graft in a Rat Partial Meniscus Defect Model

Author:

Ozeki Nobutake12,Muneta Takeshi1,Matsuta Seiya1,Koga Hideyuki1,Nakagawa Yusuke1,Mizuno Mitsuru3,Tsuji Kunikazu4,Mabuchi Yo5,Akazawa Chihiro5,Kobayashi Eiji6,Saito Tomoyuki2,Sekiya Ichiro3

Affiliation:

1. Department of Joint Surgery and Sports medicine, Yokohama, Japan

2. Department of Orthopaedic Surgery Yokohama City University, Yokohama, Japan

3. Center for Stem Cell and Regenerative Medicine Tokyo Medical and Dental University, Tokyo, Japan

4. Department of Cartilage Regeneration Graduate School of Medicine, Tokyo, Japan

5. Department of Biochemistry and Biophysics, Graduate School of Health care Science Tokyo Medical and Dental University, Tokyo, Japan

6. Department of Organ Fabrication Keio University School of Medicine, Tokyo, Japan

Abstract

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. Stem Cells  2015;33:1927–1938

Funder

Research on Regenerative Medicine for Clinical Application from the Ministry of Health, Labor and Welfare

Publisher

Oxford University Press (OUP)

Subject

Cell Biology,Developmental Biology,Molecular Medicine

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