Review| Volume 47, ISSUE 11, P2399-2406, November 2016

The roles of immune cells in bone healing; what we know, do not know and future perspectives

  • Jehan J. El-Jawhari
    Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, UK

    NIHR Biomedical Research Unit, Chapel Allerton Hospital, University of Leeds, UK

    Clinical Pathology Department, Faculty of Medicine, Mansoura University, Egypt
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  • Elena Jones
    Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, UK

    NIHR Biomedical Research Unit, Chapel Allerton Hospital, University of Leeds, UK
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  • Peter V. Giannoudis
    Corresponding author at: Academic Department of Trauma and Orthopaedic Surgery/Honorary Orthopaedic and Trauma Consultant, Leeds General Infirmary, School of Medicine, University of Leeds, UK.
    Leeds Institute of Rheumatic and Musculoskeletal Medicine, St. James Hospital, University of Leeds, UK

    NIHR Biomedical Research Unit, Chapel Allerton Hospital, University of Leeds, UK
    Search for articles by this author


      Key events occurring during the bone healing include well-orchestrated and complex interactions between immune cells, multipotential stromal cells (MSCs), osteoblasts and osteoclasts. Through three overlapping phases of this physiological process, innate and adaptive immune cells, cytokines and chemokines have a significant role to play. The aim of the escalating immune response is to achieve an osseous healing in the shortest time and with the least complications facilitating the restoration of function. The uninterrupted progression of these biological events in conjunction with a favourable mechanical environment (stable fracture fixation) remains the hallmark of successful fracture healing. When failure occurs, either the biological environment or the mechanical one could have been disrupted. Not infrequently both may be compromised. Consequently, regenerative treatments involving the use of bone autograft, allograft or synthetic matrices supplemented with MSCs are increasingly used. A better understanding of the bone biology and osteoimmunology can help to improve these evolving cell-therapy based strategies. Herein, an up to date status of the role of immune cells during the different phases of bone healing is presented. Additionally, the known and yet to know events about immune cell interactions with MSCs and osteoblasts and osteoclasts and the therapeutic implications are being discussed.


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