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  • Review Article
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Mesenchymal stem cells in joint disease and repair

Nature Reviews Rheumatology volume 9, pages 584–594 (2013)Cite this article

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Abstract

Osteoarthritis (OA), a prevalent chronic condition with a striking impact on quality of life, represents an enormous societal burden that increases greatly as populations age. Yet no approved pharmacological intervention, biologic therapy or procedure prevents the progressive destruction of the OA joint. Mesenchymal stem cells (MSCs)—multipotent precursors of connective tissue cells that can be isolated from many adult tissues, including those of the diarthrodial joint—have emerged as a potential therapy. Endogenous MSCs contribute to maintenance of healthy tissues by acting as reservoirs of repair cells or as immunomodulatory sentinels to reduce inflammation. The onset of degenerative changes in the joint is associated with aberrant activity or depletion of these cell reservoirs, leading to loss of chondrogenic potential and preponderance of a fibrogenic phenotype. Local delivery of ex vivo cultures of MSCs has produced promising outcomes in preclinical models of joint disease. Mechanistically, paracrine signalling by MSCs might be more important than differentiation in stimulating repair responses; thus, paracrine factors must be assessed as measures of MSC therapeutic potency, to replace traditional assays based on cell-surface markers and differentiation. Several early-stage clinical trials, initiated or underway in 2013, are testing the delivery of MSCs as an intra-articular injection into the knee, but optimal dose and vehicle are yet to be established.

Key Points

  • Osteoarthritis (OA) is associated with progressive and irreversible destruction of joint tissues with no defined aetiology

  • All joint tissues contain resident populations of mesenchymal stem cells (MSCs) capable of differentiating into cartilage, bone and other tissues

  • OA seems to be associated with changes in the quantity, phenotype, and differentiation potential of resident MSCs

  • Transplantation of ex vivo preparations of MSCs to the OA joint can evoke a therapeutically useful repair response in animal models of the disease

  • The repair effect mediated by delivered MSCs seems to arise as a result of paracrine responses

  • Early-stage clinical trials, initiated or underway in 2013, are testing intra-articular injection of MSCs, mostly without scaffold in the knee, but the optimal dose and vehicle have not been established

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Figure 1: Characteristics, culture phenotypes and cell-surface markers* of MSCs isolated from tissues within the knee joint.
Figure 2: Cell therapy for the treatment of osteoarthritis using bone marrow-derived MSCs.
Figure 3: Examples of MSC therapy used for the treatment of joint lesions or preclinical models of OA.

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Acknowledgements

The authors acknowledge funding support from Science Foundation Ireland (grant number 09/SRC/B1794), the European Union's 7th Framework Programme (grant numbers HEALTH-2007-B-223298 [PurStem], HEALTH-2009-1.4-3-241719 [ADIPOA] and NMP3-SL-2010-245993 [GAMBA]), and the Health Research Board of Ireland.

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  1. Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, National University of Ireland Galway, University Road, Galway, Ireland

    Frank Barry & Mary Murphy

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Both authors made substantial contributions to researching data for the article, discussions of content, writing the article, and review and/or editing of the manuscript before submission.

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F. Barry declares that he owns stocks in Osiris Therapeutics and Orbsen Therapeutics, and is a Director of Orbsen Therapeutics. M. Murphy declares that she owns stocks in Osiris Therapeutics.

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Barry, F., Murphy, M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol 9, 584–594 (2013). https://doi.org/10.1038/nrrheum.2013.109

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