Mesenchymal stem cell-derived extracellular vesicles enriched with miR-124 exhibit anti-inflammatory effects in collagen-induced arthritis

Authors

  • Zhonghua Guo Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450002, China https://orcid.org/0000-0002-9606-752X
  • Mengyuan He Graduate student Henan University of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450000, China https://orcid.org/0009-0003-0651-2808
  • Dongliang Shi Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450002, China https://orcid.org/0009-0003-1659-8772
  • Zhongbo Zhang Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450002, China https://orcid.org/0009-0007-2908-389X
  • Lisha Wang Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450002, China https://orcid.org/0009-0002-9696-4308
  • Bowen Ren Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450002, China https://orcid.org/0009-0005-6141-8392
  • Yunfei Wang Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450002, China https://orcid.org/0009-0002-0737-5588
  • Junjie Wang Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450002, China https://orcid.org/0009-0007-3182-3869
  • Shaoxiang Yang Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, 450002, China https://orcid.org/0009-0005-8334-3977
  • Hongchao Yu Department of Orthopedics, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang City, Shaanxi Province, 712000, China

DOI:

https://doi.org/10.2298/ABS240630030G

Keywords:

mesenchymal stem cells, extracellular vesicles, exosome, arthritis, cytokine

Abstract

Paper description:

  • Rheumatoid arthritis (RA) is a chronic inflammatory disease treated with limited success. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) may help by secreting anti-inflammatory factors.
  • We investigated whether human umbilical cord MSC-EVs overexpress miR-124 using lipofectamine 3000 could enhance their therapeutic potential.
  • EVs enriched with miR-124 reduced disease severity in a mouse model of arthritis, by modulating inflammatory cytokines.
  • MSC-EVs that overexpress specific miRNAs offer a promising cell-free approach for optimizing the treatment of inflammatory joint diseases.

Abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, leading to pain, swelling, stiffness, and joint damage. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) hold significant promise as therapeutic agents owing to their potent paracrine activities. This study investigated the anti-inflammatory effects of human umbilical cord-derived MSC (hUCSC)-EVs overexpressing miR-124 in collagen-induced arthritis (CIA). hUCSCs were transfected with miR-124, and hUCSC-EVs were isolated and characterized. Arthritis was induced in mice by collagen injection, followed by intravenous administration of miR-124 EVs, miR-control, or vehicle. Cytokine levels, including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β, were measured in the joints using real-time PCR by enzyme-linked immunosorbent assay (ELISA). miR-124-hUCSC-EVs showed enrichment of miR-124. In arthritic mice, intravenous treatment with miR-124 EVs significantly reduced the clinical score, increased anti-inflammatory cytokines IL-10 and TGF-β, and lowered inflammatory cytokines IL-6, TNF-α, and IL-1β in the joints. This study shows that miR-124 EVs have anti-inflammatory activity in arthritis by suppressing pro-inflammatory cytokines through miR-124 overexpression. MSC-EVs overexpressed with inflammation-modulating miRNAs offer a promising cell-free approach for treating inflammatory arthritis.

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Published

2024-12-20

How to Cite

1.
Guo Z, He M, Shi D, Zhang Z, Wang L, Ren B, Wang Y, Wang J, Yang S, Yu H. Mesenchymal stem cell-derived extracellular vesicles enriched with miR-124 exhibit anti-inflammatory effects in collagen-induced arthritis. Arch Biol Sci [Internet]. 2024Dec.20 [cited 2024Dec.30];76(4):399-407. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/10016

Issue

Vol. 76 No. 4 (2024)

Section

Articles

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Copyright (c) 2024 Zhonghua Guo , Mengyuan He, Dongliang Shi , Zhongbo Zhang, Lisha Wang, Bowen Ren, Yunfei Wang , Junjie Wang, Shaoxiang Yang , Hongchao Yu

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