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Cited by 346

The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.

Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration In Vitro

Open access
Vonk, Lucienne A., van Dooremalen, Sanne F. J., Liv, Nalan, Klumperman, Judith, Coffer, Paul J., Saris, Daniël B.F., Lorenowicz, Magdalena J.·2018·Theranostics

Abstract

Osteoarthritis (OA) is a rheumatic disease leading to chronic pain and disability with no effective treatment available.Recently, allogeneic human mesenchymal stromal/stem cells (MSC) entered clinical trials as a novel therapy for OA.Increasing evidence suggests that therapeutic efficacy of MSC depends on paracrine signalling.Here we investigated the role of extracellular vesicles (EVs) secreted by human bone marrow derived MSC (BMMSC) in human OA cartilage repair.Methods: To test the effect of BMMSC-EVs on OA cartilage inflammation, TNF-alpha-stimulated OA chondrocyte monolayer cultures were treated with BMMSC-EVs and pro-inflammatory gene expression was measured by qRT-PCR after 48 h.To assess the impact of BMMSC-EVs on cartilage regeneration, BMMSC-EVs were added to the regeneration cultures of human OA chondrocytes, which were analyzed after 4 weeks for glycosaminoglycan content by 1,9-dimethylmethylene blue (DMMB) assay.Furthermore, paraffin sections of the regenerated tissue were stained for proteoglycans (safranin-O) and type II collagen (immunostaining).Results: We show that BMMSC-EVs inhibit the adverse effects of inflammatory mediators on cartilage homeostasis.When co-cultured with OA chondrocytes, BMMSC-EVs abrogated the TNF-alpha-mediated upregulation of COX2 and pro-inflammatory interleukins and inhibited TNF-alpha-induced collagenase activity.BMMSC-EVs also promoted cartilage regeneration in vitro.Addition of BMMSC-EVs to cultures of chondrocytes isolated from OA patients stimulated production of proteoglycans and type II collagen by these cells.Conclusion: Our data demonstrate that BMMSC-EVs can be important mediators of cartilage repair and hold great promise as a novel therapeutic for cartilage regeneration and osteoarthritis.

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Metadata

Authors
Vonk, L. A., van Dooremalen, S. F. J., Liv, N., Klumperman, J., Coffer, P. J., Saris, D. B. F., & Lorenowicz, M. J.
Venue
Theranostics
Published
2018
Volume
8
Issue
4
Pages
906-920
ISSN
1838-7640 (ISSN-L)
OpenAlex
W2780538963
Cited by
346
References
51
FWCI
18.49
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration In Vitro. https://app.cochat.ai/papers/10.7150/thno.20746
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Vonk, L. A., van Dooremalen, S. F. J., Liv, N., Klumperman, J., Coffer, P. J., Saris, D. B. F., & Lorenowicz, M. J. (2018). Mesenchymal Stromal/stem Cell-derived Extracellular Vesicles Promote Human Cartilage Regeneration In Vitro. Theranostics. https://doi.org/10.7150/thno.20746

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