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From isolation to implantation: a concise review of mesenchymal stem cell therapy in bone fracture repair

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Abstract

Compromised bone-regenerating capability following a long bone fracture is often the result of reduced host bone marrow (BM) progenitor cell numbers and efficacy. Without surgical intervention, these malunions result in mobility restrictions, deformities, and disability. The clinical application of BM-derived mesenchymal stem cells (MSCs) is a feasible, minimally invasive therapeutic option to treat non-union fractures. This review focuses on novel, newly identified cell surface markers in both the mouse and human enabling the isolation and purification of osteogenic progenitor cells as well as their direct and indirect contributions to fracture repair upon administration. Furthermore, clinical success to date is summarized with commentary on autologous versus allogeneic cell sources and the methodology of cell administration. Given our clinical success to date in combination with recent advances in the identification, isolation, and mechanism of action of MSCs, there is a significant opportunity to develop improved technologies for defining therapeutic MSCs and potential to critically inform future clinical strategies for MSC-based bone regeneration.

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Abbreviations

BM:

Bone marrow

BMP:

Bone morphogenetic protein

CAR:

Chimeric antigen receptor

DBM:

Demineralized bone matrix

DTR:

Diptheria toxin receptor

eGFP:

Enhanced green fluorescent protein

EO:

Endochondral ossification

FAP:

Fibroblast activation protein alpha

HA:

Hydroxyapatite

HME:

Hematopoietic microenvironment

HSC:

Hematopoietic stem cell

IL:

Interleukin

MSC:

Mesenchymal stem cell

Mx1:

Myxovirus resistance-1

PDGFRα:

Platelet-derived growth factor receptor alpha

Sca:

Stem cell antigen

SDF-1:

Stromal cell-derived factor-1

TNF-α:

Tumor necrosis factor-alpha.

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Acknowledgments

Funding was provided by REDDSTAR: European Union FP7 HEALTH-F2-2012-305736.

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Authors and Affiliations

  1. Orbsen Therapeutics Ltd, University Road, Galway City, Ireland

    Luke Watson & Stephen J Elliman

  2. National University of Ireland Galway, University Road, Galway, Ireland

    Cynthia M Coleman

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  1. Luke Watson
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  2. Stephen J Elliman
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  3. Cynthia M Coleman
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Correspondence to Cynthia M Coleman.

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Watson, L., Elliman, S.J. & Coleman, C.M. From isolation to implantation: a concise review of mesenchymal stem cell therapy in bone fracture repair. Stem Cell Res Ther 5, 51 (2014). https://doi.org/10.1186/scrt439

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