ArticleStem cell research & therapy2021
sTNFRII-Fc modification protects human UC-MSCs against apoptosis/autophagy induced by TNF-α and enhances their efficacy in alleviating inflammatory arthritis.
Article in Stem cell research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Autophagy in Rheumatoid Arthritis: Molecular Mechanisms, Diagnostic Biomarkers, and Emerging Therapeutic Strategies.Inflammation · 2026Review
- Immunomodulatory properties of umbilical cord mesenchymal stromal cells in immune disorders: immunoregulatory functions, therapeutic progress, and engineering strategies for enhanced efficacy.Frontiers in immunology · 2026Review
- Macrophage-centred crosstalk with infiltrating immune cells in rheumatoid arthritis and its regulation by mesenchymal stem cells.Journal of translational medicine · 2025Review
- Molecular and therapeutic effects of mesenchymal stem cell-derived exosomes on autoimmune diseases.World journal of stem cells · 2025Review
- Harnessing mesenchymal stem/stromal cells-based therapies for rheumatoid arthritis: mechanisms, clinical applications, and microenvironmental interactions.Stem cell research & therapy · 2025Review
- TP-P1-Loaded Thermosensitive Hydrogel Attenuates Rheumatoid Arthritis in a Mouse Model via TLR4/NF-κB Pathway.Journal of inflammation research · 2025Article
- A Matrigel-Free 3D Chondrocytic Spheroid Model for Rheumatoid Arthritis-Associated Synoviocytes Invasion Studies.Journal of inflammation research · 2025Article
- Human spinal enthesis comparative biology of IL-17F and IL-17A reveals greater T-cell IL-17F induction and IL-23 regulation.Frontiers in immunology · 2025Article
- Mechanism and application of mesenchymal stem cells and their secreting extracellular vesicles in regulating CD4Biophysics reports · 2024Article
- Umbilical cord mesenchymal stem cells: A novel approach to intervention of ovarian ageing.Regenerative therapy · 2024Review
- Mesenchymal Stem Cells-Involved Strategies for Rheumatoid Arthritis Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Association Between Sleep Apnea Syndrome and Osteoarthritis: Insights from Bidirectional Mendelian Randomization and Bioinformatics Analysis.Nature and science of sleep · 2024Article
- Resveratrol May Reduce the Degree of Periodontitis by Regulating ERK Pathway in Gingival-Derived MSCs.International journal of molecular sciences · 2023Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- The role of TNF-α in the fate regulation and functional reprogramming of mesenchymal stem cells in an inflammatory microenvironment.Frontiers in immunology · 2023Review
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Authors and funding
10 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor necrosis factor (TNF)-α inhibitors represented by Etanercept (a fusion protein containing soluble TNF receptor II (sTNFRII) and the Fc segment of human IgG1) play a pivotal role in Rheumatoid arthritis (RA) treatment. However, long-term use increases the risk of infection and tumors for their systemic inhibition of TNF-α, which disrupts the regular physiological function of this molecular. Mesenchymal stem cells (MSCs)-based delivery system provides new options for RA treatment with their "homing" and immune-regulation capacities, whereas inflammatory environment (especially TNF-α) is not conducive to MSCs' therapeutic effects by inducing apoptosis/autophagy. Here, we constructed a strain of sTNFRII-Fc-expressing MSCs (sTNFRII-MSC), aiming to offset the deficiency of those two interventions.
methodsConstructed sTNFRII-Fc lentiviral vector was used to infect human umbilical cord-derived MSCs, and sTNFRII-MSC stable cell line was generated by monoclonal cultivation. In vitro and vivo characteristics of sTNFRII-MSC were assessed by coculture assay and an acute inflammatory model in NOD/SCID mice. The sTNFRII-MSC were transplanted into CIA model, pathological and immunological indicators were detected to evaluate the therapeutic effects of sTNFRII-MSC. The distribution of sTNFRII-MSC was determined by immunofluorescence assay. Apoptosis and autophagy were analyzed by flow cytometry, western blot and immunofluorescence.
resultssTNFRII-Fc secreted by sTNFRII-MSC present biological activity both in vitro and vivo. sTNFRII-MSC transplantation effectively alleviates mice collagen-induced arthritis (CIA) via migrating to affected area, protecting articular cartilage destruction, modulating immune balance and sTNFRII-MSC showed prolonged internal retention via resisting apoptosis/autophagy induced by TNF-α.
conclusionsTNFRII-Fc modification protects MSCs against apoptosis/autophagy induced by TNF-α, in addition to releasing sTNFRII-Fc neutralizing TNF-α to block relevant immune-inflammation cascade, and thus exert better therapeutic effects in alleviating inflammatory arthritis.
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