Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Jan 29:7:9.
doi: 10.3389/fbioe.2019.00009. eCollection 2019.

Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role of the Cell Secretome

Patrizio Mancuso  1   2 , Swarna Raman  1 , Aoife Glynn  1 , Frank Barry  1   2 , J Mary Murphy  1   2
Affiliations
Review

Mesenchymal Stem Cell Therapy for Osteoarthritis: The Critical Role of the Cell Secretome

Patrizio Mancuso et al. Front Bioeng Biotechnol. .

Abstract

Osteoarthritis (OA) is an inflammatory condition still lacking effective treatments. Mesenchymal stem/stromal cells (MSCs) have been successfully employed in pre-clinical models aiming to resurface the degenerated cartilage. In early-phase clinical trials, intra-articular (IA) administration of MSCs leads to pain reduction and cartilage protection or healing. However, the consistent lack of engraftment indicates that the observed effect is delivered through a "hit-and-run" mechanism, by a temporal release of paracrine molecules. MSCs express a variety of chemokines and cytokines that aid in repair of degraded tissue, restoration of normal tissue metabolism and, most importantly, counteracting inflammation. Secretion of therapeutic factors is increased upon licensing by inflammatory signals or apoptosis, induced by the host immune system. Trophic effectors are released as soluble molecules or carried by extracellular vesicles (ECVs). This review provides an overview of the functions and mechanisms of MSC-secreted molecules found to be upregulated in models of OA, whether using in vitro or in vivo models.

Keywords: chondroprotection; immunomodulation; mesenchymal stem cells; osteoarthristis; paracrine action; secretome.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Proposed mechanism of action for tissue repair by endogenous MSCs.
Figure 2
Figure 2
Representation of the immunomodulatory effects of apoptotic MSCs.
See this image and copyright information in PMC

References

    1. Aggarwal S., Pittenger M. F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105, 1815–1822. 10.1182/blood-2004-04-1559 - DOI - PubMed
    1. Aigner T., Kim H. A., Roach H. I. (2004). Apoptosis in osteoarthritis. Rheum Dis Clin North Am. 30, 639–653, xi. 10.1016/j.rdc.2004.04.002 - DOI - PubMed
    1. Ankrum J. A., Ong J. F., Karp J. M. (2014). Mesenchymal stem cells: immune evasive, not immune privileged. Nat. Biotechnol. 32, 252–260. 10.1038/nbt.2816 - DOI - PMC - PubMed
    1. Ayral X., Pickering E. H., Woodworth T. G., Mackillop N., Dougados M. (2005). Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis – results of a 1 year longitudinal arthroscopic study in 422 patients. Osteoarthr. Cartil. 13, 361–367. 10.1016/j.joca.2005.01.005 - DOI - PubMed
    1. Baker K., Grainger A., Niu J., Clancy M., Guermazi A., Crema M., et al. . (2010). Relation of synovitis to knee pain using contrast-enhanced MRIs. Ann. Rheum. Dis. 69, 1779–1783. 10.1136/ard.2009.121426 - DOI - PMC - PubMed

LinkOut - more resources