ArticleThe journal of gene medicine2018
Cytokine-induced interleukin-1 receptor antagonist protein expression in genetically engineered equine mesenchymal stem cells for osteoarthritis treatment.
Article in The journal of gene medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Species-specific inflammatory responses of chondrocytes: Toward evidence-based model selection in OA research.iScience · 2026Article
- Alpha-2-Macroglobulin-Enriched Plasma Modulates Inflammatory and Proteolytic Pathways in Experimental Equine Musculoskeletal Models.Animals : an open access journal from MDPI · 2026Article
- 3D-Printed core-shell tablet for effective oral delivery of AT-MSC secretome in inflammatory bowel disease therapy.Drug delivery and translational research · 2026Article
- Single Intra-Articular Anakinra (IL-1Ra) Versus Betamethasone in Rabbit Post-Traumatic Knee Osteoarthritis: IL-8 Suppression and Chondrocyte Viability.Cell biochemistry and function · 2026Article
- Establishment and characterization of an inflammatory cartilaginous organoids model for organoid transplantation study.Journal of orthopaedic translation · 2025Article
- A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine.Osteoarthritis and cartilage · 2025Article
- Mesenchymal stem cells for osteoarthritis: Recent advances in related cell therapy.Bioengineering & translational medicine · 2025Review
- IL-1 receptor antagonist: etiological and drug delivery systems overview.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- A programmable arthritis-specific receptor for guided articular cartilage regenerative medicine.bioRxiv : the preprint server for biology · 2024Article
- Engineering approaches for RNA-based and cell-based osteoarthritis therapies.Nature reviews. Rheumatology · 2024Review
- Microencapsulated stem cells reduce cartilage damage in a material dependent manner following minimally invasive intra-articular injection in an OA rat model.Materials today. Bio · 2023Article
- Interleukin-1 receptor antagonist: a promising cytokine against human squamous cell carcinomas.Heliyon · 2023Review
- Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review.Frontiers in medicine · 2023Article
- Gene therapy approaches for equine osteoarthritis.Frontiers in veterinary science · 2022Review
- Immunoengineering the next generation of arthritis therapies.Acta biomaterialia · 2021Review
- Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy.Frontiers in cell and developmental biology · 2021Review
- Cytokine-induced interleukin-1 receptor antagonist protein expression in genetically engineered equine mesenchymal stem cells for osteoarthritis treatment.The journal of gene medicine · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA combination of tissue engineering methods employing mesenchymal stem cells (MSCs) together with gene transfer takes advantage of innovative strategies and highlights a new approach for targeting osteoarthritis (OA) and other cartilage defects. Furthermore, the development of systems allowing tunable transgene expression as regulated by natural disease-induced substances is highly desirable.
methodsBone marrow-derived equine MSCs were transduced with a lentiviral vector expressing interleukin-1 receptor antagonist (IL-1Ra) gene under the control of an inducible nuclear factor-kappa B-responsive promoter and IL-1Ra production upon pro-inflammatory cytokine stimulation [tumor necrosis factor (TNF)α, interleukin (IL)-1β] was analysed. To assess the biological activity of the IL-1Ra protein that was produced and the therapeutic effect of IL-1Ra-expressing MSCs (MSC/IL-1Ra), cytokine-based two- and three-dimensional in vitro models of osteoarthritis using equine chondrocytes were established and quantitative real-time polymerase chain reaction (PCR) analysis was used to measure the gene expression of aggrecan, collagen IIA1, interleukin-1β, interleukin-6, interleukin-8, matrix metalloproteinase-1 and matrix metalloproteinase-13.
resultsA dose-dependent increase in IL-1Ra expression was found in MSC/IL-1Ra cells upon TNFα administration, whereas stimulation using IL-1β did not lead to IL-1Ra production above the basal level observed in nonstimulated cells as a result of the existing feedback loop. Repeated cycles of induction allowed on/off modulation of transgene expression. In vitro analyses revealed that IL-1Ra protein present in the conditioned medium from MSC/IL-1Ra cells blocks OA onset in cytokine-treated equine chondrocytes and co-cultivation of MSC/IL-1Ra cells with osteoarthritic spheroids alleviates the severity of the osteoarthritic changes.
conclusionsThus, pro-inflammatory cytokine induced IL-1Ra protein expression from genetically modified MSCs might represent a promising strategy for osteoarthritis treatment.
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