ArticleStem cell research & therapy2025
Human spindle-shaped urine-derived stem cell exosomes alleviate severe fatty liver ischemia-reperfusion injury by inhibiting ferroptosis via GPX4.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Nanomaterial-Based Precision Drug Delivery for Advanced Nephrology Therapy: A Systematic Review.International journal of nanomedicine · 2026Pooled it
- Steatotic liver-derived extracellular vesicles deliver ACSL4 to potentiate hepatic ischemia-reperfusion injury by orchestrating a ferroptosis-mitochondrial apoptosis cascade.Genes & diseases · 2027Article
- Galectin-3 Promotes Graft Injury via NLRP3 Pyroptosis in Steatotic Liver Transplantation: A Therapeutic Target for Donor Optimization.Journal of clinical and translational hepatology · 2026Article
- LDLRJournal of clinical and translational hepatology · 2026Article
- The Mechanism of G Protein-Coupled Receptor Regulation of Ferroptosis in Hepatic Ischemia-Reperfusion Injury.International journal of molecular sciences · 2026Review
- Spirulina Preconditioning Attenuates Ischemia-Reperfusion Injury in a Steatotic Rat Liver Model.Antioxidants (Basel, Switzerland) · 2026Article
- Mesenchymal stem cell-derived extracellular vesicles for disease therapy by regulating ferroptosis: focus on diabetes mellitus and diabetic complications.Stem cell research & therapy · 2025Review
- Targeting ferroptosis as a therapeutic strategy for hepatotoxicity.Toxicology reports · 2025Review
- Hydroxysafflor Yellow A Mitigates Sepsis-Induced Pulmonary and Intestinal Injury by Inhibiting TP53 Mediated Ferroptosis.Infection and drug resistance · 2025Article
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Authors and funding
14 authors.
Funding
Abstract
backgroundSevere hepatic steatosis can exacerbate Ischemia-reperfusion injury (IRI), potentially leading to early graft dysfunction and primary non-function. In this study, we investigated the heterogeneity of different subpopulations of Urine-derived stem cells (USCs) to explore the most suitable cell subtype for treating severe steatotic liver IRI.
methodsThis study utilized scRNA-seq and Bulk RNA-seq to investigate the transcriptional heterogeneity between Spindle-shaped USCs (SS-USCs) and Rice-shaped USCs (RS-USCs). Additionally, rat fatty Liver transplantation (LT) model, mouse fatty liver IRI model, and Steatotic Hepatocyte Hypoxia-Reoxygenation (SHP-HR) model were constructed. Extracellular vesicles derived from SS-USCs and RS-USCs were isolated and subjected to mass spectrometry analysis. The therapeutic effects of Spindle-shaped USCs Exosomes (SS-USCs-Exo) and Rice-shaped USCs Exosomes (RS-USCs-Exo) were explored, elucidating their potential mechanisms in inhibiting ferroptosis and alleviating IRI.
resultsMultiple omics analyses confirmed that SS-USCs possess strong tissue repair and antioxidant capabilities, while RS-USCs have the potential to differentiate towards specific directions such as the kidney, nervous system, and skeletal system, particularly showing great application potential in renal system reconstruction. Further experiments demonstrated in vivo and in vitro models confirming that SS-USCs and SS-USCs-Exo significantly inhibit ferroptosis and alleviate severe fatty liver IRI, whereas the effects of RS-USCs/RS-USCs-Exo are less pronounced. Analysis comparing the proteomic differences between SS-USCs-Exo and RS-USCs-Exo revealed that SS-USCs-Exo primarily inhibit ferroptosis and improve cellular viability by secreting exosomes containing Glutathione Peroxidase 4 (GPX4) protein. This highlights the most suitable cell subtype for treating severe fatty liver IRI.
conclusionsSS-USCs possess strong tissue repair and antioxidant capabilities, primarily alleviating ferroptosis in the donor liver of fatty liver through the presence of GPX4 protein in their exosomes. This highlights SS-USCs as the most appropriate cell subtype for treating severe fatty liver IRI.
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