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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.

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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

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