ArticleScience advances2020
Glutathione dynamics determine the therapeutic efficacy of mesenchymal stem cells for graft-versus-host disease via CREB1-NRF2 pathway.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 61 citations in OpenAlex.
- Preventive hyperbaric oxygen therapy improves acute graft-versus-host disease by activating the Nrf2/HO-1 pathway.Frontiers in immunology · 2025Trial
- Targeted KEAP1 disruption enhances antioxidant defense and mesenchymal stromal cell therapy for chronic limb-threatening ischemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Machine learning-based integration of transcriptome and digital pathology for predicting chemoresistance in muscle-invasive bladder cancer.Experimental & molecular medicine · 2026Article
- Regulation of stress tolerance by CREB1 sustains multiple myeloma cell survival.Cell death & disease · 2026Article
- Multi-layered integrated shielding: engineering ferroptosis-resistant mesenchymal stem cells for precision therapy of intervertebral disc degeneration.Apoptosis : an international journal on programmed cell death · 2026Review
- Systemic control of HNF1B-driven redox homeostasis by N6-adenosine methylation.Nucleic acids research · 2026Article
- Mesenchymal Stromal Cells: Bridging the Gaps in Hematologic Disease Therapy.Stem cell reviews and reports · 2026Review
- Dual Specificity Phosphatase 27 Regulates Pluripotency and Meso-Endodermal Differentiation by Interacting with Transcription Factor CP2 Like-1 in Embryonic Stem Cells.International journal of stem cells · 2025Article
- Review
- Mesenchymal Stromal Cells and Graft-versus-Host Disease: Preclinical and Clinical Studies.Stem cell reviews and reports · 2025Review
- Panoramic lead-immune system interactome reveals diversified mechanisms of immunotoxicity upon chronic lead exposure.Cell biology and toxicology · 2025Article
- Assessment of the Therapeutic Effectiveness of Glutathione-Enhanced Mesenchymal Stem Cells in Rat Models of Chronic Bladder Ischemia-Induced Overactive Bladder and Detrusor Underactivity.International journal of stem cells · 2025Article
- Targeting ferroptosis: opportunities and challenges of mesenchymal stem cell therapy for type 1 diabetes mellitus.Stem cell research & therapy · 2025Review
- Insulin-Like Growth Factor 2 Secreted from Mesenchymal Stem Cells with High Glutathione Levels Alleviates Osteoarthritis via Paracrine Rejuvenation of Senescent Chondrocytes.Biomaterials research · 2025Article
- Article
- Ex vivo-generated human CD1cMolecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Mesenchymal stem cells with an enhanced antioxidant capacity integrate as smooth muscle cells in a model of diabetic detrusor underactivity.Clinical and translational medicine · 2024Article
- Glutathione Dynamics in the Tumor Microenvironment: A Potential Target of Cancer Stem Cells and T Cells.International journal of stem cells · 2024Review
- hPMSCs Regulate the Level of TNF-α and IL-10 in Th1 Cells and Improve Hepatic Injury in a GVHD Mouse Model via CD73/ADO/Fyn/Nrf2 Axis.Inflammation · 2024Article
- Glutathione dynamics is a potential predictive and therapeutic trait for neoadjuvant chemotherapy response in bladder cancer.Cell reports. Medicine · 2023Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutathione (GSH), the most abundant nonprotein thiol functioning as an antioxidant, plays critical roles in maintaining the core functions of mesenchymal stem cells (MSCs), which are used as a cellular immunotherapy for graft-versus-host disease (GVHD). However, the role of GSH dynamics in MSCs remains elusive. Genome-wide gene expression profiling and high-throughput live-cell imaging assays revealed that CREB1 enforced the GSH-recovering capacity (GRC) of MSCs through NRF2 by directly up-regulating NRF2 target genes responsible for GSH synthesis and redox cycling. MSCs with enhanced GSH levels and GRC mediated by CREB1-NRF2 have improved self-renewal, migratory, anti-inflammatory, and T cell suppression capacities. Administration of MSCs overexpressing CREB1-NRF2 target genes alleviated GVHD in a humanized mouse model, resulting in improved survival, decreased weight loss, and reduced histopathologic damages in GVHD target organs. Collectively, these findings demonstrate the molecular and functional importance of the CREB1-NRF2 pathway in maintaining MSC GSH dynamics, determining therapeutic outcomes for GVHD treatment.
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