Mesenchymal Stem Cells Reduce Intervertebral Disc Fibrosis and Facilitate Repair

Authors

  • Victor Y.L. Leung,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
    2. Department of Biochemistry, The University of Hong Kong, Hong Kong SAR, People's Republic of China
    3. Centre for Reproduction, Development, and Growth, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Darwesh M.K. Aladin,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
    2. Mechanobiology Institute, National University of Singapore, Singapore
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  • Fengjuan Lv,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Vivian Tam,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Yi Sun,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Roy Y.C. Lau,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Siu-Chun Hung,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Alfonso H.W. Ngan,

    1. Department of Mechanical Engineering, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Bin Tang,

    1. Department of Micro-nano Materials and Devices, South University of Science and Technology of China, Guangzhou, People's Republic of China
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  • Chwee Teck Lim,

    1. Mechanobiology Institute, National University of Singapore, Singapore
    2. Department of Bioengineering, National University of Singapore, Singapore
    3. Department of Mechanical Engineering, National University of Singapore, Singapore
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  • Ed X. Wu,

    1. Department of Electrical & Electronic Engineering, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Keith D.K. Luk,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • William W. Lu,

    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
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  • Koichi Masuda,

    1. Department of Orthopaedic Surgery, University of California, San Diego, California, USA
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  • Danny Chan,

    Corresponding author
    1. Department of Biochemistry, The University of Hong Kong, Hong Kong SAR, People's Republic of China
    2. Centre for Reproduction, Development, and Growth, The University of Hong Kong, Hong Kong SAR, People's Republic of China
    • Correspondence: Kenneth M.C. Cheung, M.D., Department of Orthopaedics and Traumatology, The University of Hong Kong Medical Centre, Queen Mary Hospital, Pokfulam Road, Pokfulam, Hong Kong SAR, People's Republic of China. Telephone: +852-2855-4254; Fax: +852-2817-4392; e-mail: cheungmc@hku.hk; or Danny Chan, Ph.D., Department of Biochemistry, 3/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China. Telephone: +852-2819-9482; Fax: +852-2855-1254; e-mail: chand@hku.hk

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  • Kenneth M.C. Cheung

    Corresponding author
    1. Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China
    2. Centre for Reproduction, Development, and Growth, The University of Hong Kong, Hong Kong SAR, People's Republic of China
    • Correspondence: Kenneth M.C. Cheung, M.D., Department of Orthopaedics and Traumatology, The University of Hong Kong Medical Centre, Queen Mary Hospital, Pokfulam Road, Pokfulam, Hong Kong SAR, People's Republic of China. Telephone: +852-2855-4254; Fax: +852-2817-4392; e-mail: cheungmc@hku.hk; or Danny Chan, Ph.D., Department of Biochemistry, 3/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, People's Republic of China. Telephone: +852-2819-9482; Fax: +852-2855-1254; e-mail: chand@hku.hk

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Abstract

Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to society. There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture-induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow-derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self-repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases. Stem Cells 2014;32:2164–2177

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