ArticleCell communication and signaling : CCS2022
Mesenchymal stem cells protect against TBI-induced pyroptosis in vivo and in vitro through TSG-6.
Article in Cell communication and signaling : CCS, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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20 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Evolution of mesenchymal stem cell therapies for traumatic brain injury: A decade of advances, mechanisms, and translational prospects.Cell transplantationPooled it
- Rosiglitazone alleviates white matter injury by inhibiting NLRP3/capspase-1 mediated microglial pyroptosis via downregulating KLF4.Experimental brain research · 2026Article
- Dynamic Tuning of MSC-Based Scaffolds for Neurological Protection After Brain or CNS Injury.Life (Basel, Switzerland) · 2026Review
- Microglia-specific NLRP3 inhibition mitigates hippocampal neuroinflammation and cognitive deficits after hemorrhagic shock with resuscitation.Behavioral and brain functions : BBF · 2026Article
- Microglia-Targeted Biomimetic Tetrahedral Framework Nucleic Acid Nanovesicles for Synergistic Treatment of Sepsis-Associated Encephalopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bone marrow mesenchymal stem cell-derived TSG-6 regulates microglial pyroptosis and alleviates bone cancer pain by inhibiting the NLRP3 inflammasome.Stem cell research & therapy · 2026Article
- USP4 modulates ZBP1 ubiquitination to regulate microglial PANoptosis and functional outcomes following traumatic brain injury.Cell death and differentiation · 2026Article
- Mesenchymal stem cells and secretome as modulators of neuroinflammation in neurological disorders.Journal of translational medicine · 2026Review
- Research progress on the role of mesenchymal stem cells in pyroptosis in sepsis.Stem cell research & therapy · 2025Review
- E2 pretreatment alleviates aggregation of intravenously injected mesenchymal stem cells in TBI by regulating BRG1 to affect adhesion.Stem cell research & therapy · 2025Article
- IFI204 in microglia mediates traumatic brain injury-induced mitochondrial dysfunction and pyroptosis via SENP7 interaction.Cell biology and toxicology · 2025Article
- Role of damage-associated molecular patterns in the pathogenesis and therapeutics of traumatic brain injury.Burns & trauma · 2025Review
- Beneficial Effects of Human Schwann Cell-Derived Exosomes in Mitigating Secondary Damage After Penetrating Ballistic-Like Brain Injury.Journal of neurotrauma · 2024Article
- Mesenchymal stem cells ameliorate inflammation and pyroptosis in diabetic cardiomyopathy via the miRNA-223-3p/NLRP3 pathway.Diabetology & metabolic syndrome · 2024Article
- hP-MSCs attenuate severe acute pancreatitis in mice via inhibiting NLRP3 inflammasome-mediated acinar cell pyroptosis.Apoptosis : an international journal on programmed cell death · 2024Article
- Ginkgolide A attenuated apoptosis via inhibition of oxidative stress in mice with traumatic brain injury.Heliyon · 2024Article
- Targeting pyroptosis with nanoparticles to alleviate neuroinflammatory for preventing secondary damage following traumatic brain injury.Science advances · 2024Article
- Neuroprotective Effect of Hydrogen Sulfide Subchronic Treatment Against TBI-Induced Ferroptosis and Cognitive Deficits Mediated Through Wnt Signaling Pathway.Cellular and molecular neurobiology · 2023Article
- The Crosstalk between Mesenchymal Stromal/Stem Cells and Hepatocytes in Homeostasis and under Stress.International journal of molecular sciences · 2023Review
- A novel organotypic cortical slice culture model for traumatic brain injury: molecular changes induced by injury and mesenchymal stromal cell secretome treatment.Frontiers in cellular neuroscience · 2023Article
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Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPyroptosis, especially microglial pyroptosis, may play an important role in central nervous system pathologies, including traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs), such as human umbilical cord MSCs (hUMSCs), has been a focus of brain injury treatment. Recently, MSCs have been found to play a role in many diseases by regulating the pyroptosis pathway. However, the effect of MSC transplantation on pyroptosis following TBI remains unknown. Tumor necrosis factor α stimulated gene 6/protein (TSG-6), a potent anti-inflammatory factor expressed in many cell types including MSCs, plays an anti-inflammatory role in many diseases; however, the effect of TSG-6 secreted by MSCs on pyroptosis remains unclear.
methodsMice were subjected to controlled cortical impact injury in vivo. To assess the time course of pyroptosis after TBI, brains of TBI mice were collected at different time points. To study the effect of TSG-6 secreted by hUMSCs in regulating pyroptosis, normal hUMSCs, sh-TSG-6 hUMSCs, or different concentrations of rmTSG-6 were injected intracerebroventricularly into mice 4 h after TBI. Neurological deficits, double immunofluorescence staining, presence of inflammatory factors, cell apoptosis, and pyroptosis were assessed. In vitro, we investigated the anti-pyroptosis effects of hUMSCs and TSG-6 in a lipopolysaccharide/ATP-induced BV2 microglial pyroptosis model.
resultsIn TBI mice, the co-localization of Iba-1 (marking microglia/macrophages) with NLRP3/Caspase-1 p20/GSDMD was distinctly observed at 48 h. In vivo, hUMSC transplantation or treatment with rmTSG-6 in TBI mice significantly improved neurological deficits, reduced inflammatory cytokine expression, and inhibited both NLRP3/Caspase-1 p20/GSDMD expression and microglial pyroptosis in the cerebral cortices of TBI mice. However, the therapeutic effect of hUMSCs on TBI mice was reduced by the inhibition of TSG-6 expression in hUMSCs. In vitro, lipopolysaccharide/ATP-induced BV2 microglial pyroptosis was inhibited by co-culture with hUMSCs or with rmTSG-6. However, the inhibitory effect of hUMSCs on BV2 microglial pyroptosis was significantly reduced by TSG-6-shRNA transfection.
conclusionIn TBI mice, microglial pyroptosis was observed. Both in vivo and in vitro, hUMSCs inhibited pyroptosis, particularly microglial pyroptosis, by regulating the NLRP3/Caspase-1/GSDMD signaling pathway via TSG-6. Video Abstract.
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