ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Suppressing Mesenchymal Stromal Cell Ferroptosis Via Targeting a Metabolism-Epigenetics Axis Corrects their Poor Retention and Insufficient Healing Benefits in the Injured Liver Milieu.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Engineered NestinJournal of extracellular vesicles · 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
- Branched-chain amino acid transaminases as promising targets in tumor therapy.Frontiers in cell and developmental biology · 2026Review
- ROS-responsive cellular vesicles with ferroptosis-targeting siACMSD delivery for acute kidney injury therapy.Theranostics · 2026Article
- Inducing ferroptosis to improve cancer therapy: a promising tool for enhancing immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Research progress on the mechanism of tumor cell ferroptosis regulation by epigenetics.Epigenetics · 2025Review
- Effects and mechanisms of MSCs and MSC-derived exosomes in regulating ferroptosis.Journal of physiology and biochemistry · 2025Review
- Targeting ferroptosis: opportunities and challenges of mesenchymal stem cell therapy for type 1 diabetes mellitus.Stem cell research & therapy · 2025Review
- Biomimetic Vascularized iPSC-Hepatocyte Spheroids for Liver Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting ferroptosis to enhance the efficacy of mesenchymal stem cell-based treatments for intervertebral disc degeneration.International journal of biological sciences · 2025Review
- Protective effects of α-ketoglutaric acid on palmitic acid-induced deterioration in sheep endometrial epithelial cells via ferroptosis inhibition.Frontiers in veterinary science · 2025Article
- Human umbilical cord mesenchymal stem cells restore chemotherapy-induced premature ovarian failure by inhibiting ferroptosis in vitro ovarian culture system.Reproductive biology and endocrinology : RB&E · 2024Article
- Pharmacokinetic characteristics of mesenchymal stem cells in translational challenges.Signal transduction and targeted therapy · 2024Review
- Heme oxygenase 1-mediated ferroptosis in Kupffer cells initiates liver injury during heat stroke.Acta pharmaceutica Sinica. B · 2024Article
- RSL3 enhances ROS-mediated cell apoptosis of myelodysplastic syndrome cells through MYB/Bcl-2 signaling pathway.Cell death & disease · 2024Article
- Enhancing mesenchymal stem cell survival and homing capability to improve cell engraftment efficacy for liver diseases.Stem cell research & therapy · 2023Review
- Suppressing Mesenchymal Stromal Cell Ferroptosis Via Targeting a Metabolism-Epigenetics Axis Corrects their Poor Retention and Insufficient Healing Benefits in the Injured Liver Milieu.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Research progress on branched-chain amino acid aminotransferases.Frontiers in genetics · 2023Review
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Mesenchymal stromal cell (MSC) implantation is a promising option for liver repair, but their poor retention in the injured liver milieu critically blunts therapeutic effects. The aim is to clarify the mechanisms underlying massive MSC loss post-implantation and establish corresponding improvement strategies. MSC loss primarily occurs within the initial hours after implantation into the injured liver milieu or under reactive oxygen species (ROS) stress. Surprisingly, ferroptosis is identified as the culprit for rapid depletion. In ferroptosis- or ROS-provoking MSCs, branched-chain amino acid transaminase-1 (BCAT1) is dramatically decreased, and its downregulation renders MSC susceptible to ferroptosis via suppressing the transcription of glutathione peroxidase-4 (GPX4), a vital ferroptosis defensing enzyme. BCAT1 downregulation impedes GPX4 transcription via a rapid-responsive metabolism-epigenetics coordinating mechanism, involving α-ketoglutarate accumulation, histone 3 lysine 9 trimethylation loss, and early growth response protein-1 upregulation. Approaches to suppress ferroptosis (e.g., incorporating ferroptosis inhibitors in injection solvent and overexpressing BCAT1) significantly improve MSC retention and liver-protective effects post-implantation. This study provides the first evidence indicating that excessive MSC ferroptosis is the nonnegligible culprit for their rapid depletion and insufficient therapeutic efficacy after implantation into the injured liver milieu. Strategies suppressing MSC ferroptosis are conducive to optimizing MSC-based therapy.
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Registered trials
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.