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Functional and Molecular Analysis of Human Osteoarthritic Chondrocytes Treated with Bone Marrow-Derived MSC-EVs

Lookup NU author(s): Annachiara Scalzone, Dr Rolando Berlinguer PalminiORCiD, Professor Anne Dickinson, Dr Xiao WangORCiD, Dr Rachel CrosslandORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2024 by the authors.Osteoarthritis (OA) is a degenerative joint disease, causing impaired mobility. There are currently no effective therapies other than palliative treatment. Mesenchymal stromal cells (MSCs) and their secreted extracellular vesicles (MSC-EVs) have shown promise in attenuating OA progression, promoting chondral regeneration, and modulating joint inflammation. However, the precise molecular mechanism of action driving their beneficial effects has not been fully elucidated. In this study, we analyzed MSC-EV-treated human OA chondrocytes (OACs) to assess viability, proliferation, migration, cytokine and catabolic protein expression, and microRNA and mRNA profiles. We observed that MSC-EV-treated OACs displayed increased metabolic activity, proliferation, and migration compared to the controls. They produced decreased proinflammatory (Il-8 and IFN-γ) and increased anti-inflammatory (IL-13) cytokines, and lower levels of MMP13 protein coupled with reduced expression of MMP13 mRNA, as well as negative microRNA regulators of chondrogenesis (miR-145-5p and miR-21-5p). In 3D models, MSC-EV-treated OACs exhibited enhanced chondrogenesis-promoting features (elevated sGAG, ACAN, and aggrecan). MSC-EV treatment also reversed the pathological impact of IL-1β on chondrogenic gene expression and extracellular matrix component (ECM) production. Finally, MSC-EV-treated OACs demonstrated the enhanced expression of genes associated with cartilage function, collagen biosynthesis, and ECM organization and exhibited a signature of 24 differentially expressed microRNAs, associated with chondrogenesis-associated pathways and ECM interactions. In conclusion, our data provide new insights on the potential mechanism of action of MSC-EVs as a treatment option for early-stage OA, including transcriptomic analysis of MSC-EV-treated OA, which may pave the way for more targeted novel therapeutics.

Publication metadata

Author(s): Scalzone A, Sanjurjo-Rodriguez C, Berlinguer-Palmini R, Dickinson AM, Jones E, Wang X-N, Crossland RE

Publication type: Article

Publication status: Published

Journal: Bioengineering

Year: 2024

Volume: 11

Issue: 4

Print publication date: 01/04/2024

Online publication date: 17/04/2024

Acceptance date: 22/03/2024

Date deposited: 13/05/2024

ISSN (electronic): 2306-5354

Publisher: Multidisciplinary Digital Publishing Institute (MDPI)


DOI: 10.3390/bioengineering11040388


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Funder referenceFunder name
21156VERSUS Arthritis (formerly Arthritis Research UK)
Versus Arthritis