ArticleCell death & disease2020
Chlorzoxazone, a small molecule drug, augments immunosuppressive capacity of mesenchymal stem cells via modulation of FOXO3 phosphorylation.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Clinical applications of mesenchymal stromal cell-based therapies for pulmonary diseases: An Update and Concise Review.International journal of medical sciences · 2021Pooled it
- Mesenchymal Stem Cells Attenuate Diabetic Nephropathy by Suppressing the ERK-Ferroptosis-ROS Axis.International journal of molecular sciences · 2026Article
- In vitro assays for investigating the immunomodulatory properties of human mesenchymal stromal cells.Stem cell research & therapy · 2026Review
- Research progress on the mechanism of FOXO protein in sepsis.Apoptosis : an international journal on programmed cell death · 2026Review
- Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review).International journal of molecular medicine · 2025Review
- Identification of glutamine as a potential therapeutic target in dry eye disease.Signal transduction and targeted therapy · 2025Article
- Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Mesenchymal stem cells under epigenetic control - the role of epigenetic machinery in fate decision and functional properties.Cell death & disease · 2023Review
- Immune microenvironment: novel perspectives on bone regeneration disorder in osteoradionecrosis of the jaws.Cell and tissue research · 2023Review
- Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function: implication of miRNAs and microvesicles.Military Medical Research · 2023Article
- Pretreated Mesenchymal Stem Cells and Their Secretome: Enhanced Immunotherapeutic Strategies.International journal of molecular sciences · 2023Review
- Characteristics and regulation of mesenchymal stem cell plasticity by the microenvironmentGenes & diseases · 2022Review
- Recent advances to enhance the immunomodulatory potential of mesenchymal stem cells.Frontiers in immunology · 2022Review
- Strategies for the induction of anti-inflammatory mesenchymal stem cells and their application in the treatment of immune-related nephropathy.Frontiers in medicine · 2022Review
- Inflammation, a common mechanism in frailty and COVID-19, and stem cells as a therapeutic approach.Stem cells translational medicine · 2021Review
- Screening and identification of potential biomarkers and therapeutic drugs in melanoma via integrated bioinformatics analysis.Investigational new drugs · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nowadays, immune diseases are a large burden in healthcare. Mesenchymal stem cells (MSCs) have prominent ability in immunomodulation and have been applicated on treating many immune-related diseases. However, the clinical outcomes can be disparate and sometimes completely counterproductive beyond explanation of cell heterogeneity. The theory of immunomodulation plasticity in MSCs has then emerged to explain that MSCs can be induced into proinflammatory MSC1 or anti-inflammatory MSC2 responding to different immune environment. It would be safer and more efficient if we could induce MSCs into a certain immune phenotype, in most cases MSC2, prior to medical treatment. In this study, we screened and identified a classical FDA-approved drug, chlorzoxazone (CZ). Unlike traditional method induced by IFN-γ, CZ can induce MSC into MSC2 phenotype and enhance the immunosuppressive capacity without elevation of immunogenicity of MSCs. CZ-treated MSCs can better inhibit T cells activation and proliferation, promote expression of IDO and other immune mediators in vitro, and alleviate inflammatory infiltration and tissue damage in acute kidney injury rat model more effectively. Moreover, we discovered that CZ modulates phosphorylation of transcriptional factor forkhead box O3 (FOXO3) independent of classical AKT or ERK signaling pathways, to promote expression of downstream immune-related genes, therefore contributing to augmentation of MSCs immunosuppressive capacity. Our study established a novel and effective approach to induce MSC2, which is ready for clinical application.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.