ArticleStem cell research & therapy2020
Adipose mesenchymal stem cell transplantation alleviates spinal cord injury-induced neuroinflammation partly by suppressing the Jagged1/Notch pathway.
Article in Stem cell research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 3 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 3 syntheses or guidelines pooled it, 67 citations in OpenAlex.
- Therapeutic efficacy of mesenchymal stem cells for abdominal aortic aneurysm: a meta-analysis of preclinical studies.Stem cell research & therapy · 2022Pooled it
- Effectiveness and mechanisms of adipose-derived stem cell therapy in animal models of Parkinson's disease: a systematic review and meta-analysis.Translational neurodegeneration · 2021Pooled it
- Mesenchymal Stem Cells for the Treatment of Spinal Cord Injury in Rat Models: A Systematic Review and Network Meta-Analysis.Cell transplantationPooled it
- Advances in the clinical application of mesenchymal stem cells for neurological disorders.Stem cell research & therapy · 2026Review
- Notch Signaling in Spinal Cord Injury: Mechanistic Insights and Therapeutic Perspectives.Molecular neurobiology · 2026Review
- STAT3 Signaling in Spinal Cord Injury: Neurochemical Mechanisms Linking Neuroinflammation, Mitochondrial Stress, and Glial Remodeling.Neurochemical research · 2026Review
- Restoring neuroplasticity after CNS trauma: cell therapy approaches in spinal cord and traumatic brain injury.Journal of translational medicine · 2026Review
- Adipose tissue-derived stromal cells enhance glycolytic metabolism in injured nerve cells via the FOXK1-HK2 axis for spinal cord injury repair.Journal of translational medicine · 2026Article
- RNA Interference and Its Key Targets for Spinal Cord Injury Therapy: What Is Known So Far?International journal of molecular sciences · 2025Review
- Investigation into the sensitivity of adipocytes mediated by the major vault protein (MVP) to chemotherapy for triple-negative breast cancer.Translational cancer research · 2025Article
- Mesenchymal stem cells in treating human diseases: molecular mechanisms and clinical studies.Signal transduction and targeted therapy · 2025Review
- Macrophage polarization-related gene SOAT1 is involved in inflammatory response and functional recovery after spinal cord injury.Molecular and cellular biochemistry · 2025Article
- Animal Models of Spinal Cord Injury.Biomedicines · 2025Review
- DLK1-expressing neural progenitor cells promote tissue repair and functional recovery after cervical spinal cord injury.Stem cells translational medicine · 2025Article
- Autophagy modulation by hADSCs and green light therapy alleviates inflammation and promotes functional recovery after spinal cord injury.Stem cell research & therapy · 2025Article
- Crosstalk Between H-Type Vascular Endothelial Cells and Macrophages: A Potential Regulator of Bone Homeostasis.Journal of inflammation research · 2025Review
- Advancements in Antioxidant-Based Therapeutics for Spinal Cord Injury: A Critical Review of Strategies and Combination Approaches.Antioxidants (Basel, Switzerland) · 2024Review
- Progression of mesenchymal stem cell regulation on imbalanced microenvironment after spinal cord injury.Stem cell research & therapy · 2024Review
- The Effect of Tissue Inhibitor of Metalloproteinases on Scar Formation after Spinal Cord Injury.Cells · 2024Review
- Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe therapeutic effects of adipose-derived mesenchymal stem cell (ADSC) transplantation have been demonstrated in several models of central nervous system (CNS) injury and are thought to involve the modulation of the inflammatory response. However, the exact underlying molecular mechanism is poorly understood. Activation of the Jagged1/Notch signaling pathway is thought to involve inflammatory and gliotic events in the CNS. Here, we elucidated the effect of ADSC transplantation on the inflammatory reaction after spinal cord injury (SCI) and the potential mechanism mediated by Jagged1/Notch signaling pathway suppression.
methodsTo evaluate the therapeutic effects of ADSC treatment and the potential inhibitory effects of ADSCs on Notch signaling, mice were subjected to contusion SCI, and GFP-labeled ADSCs were injected into the lesion site immediately after the injury. Locomotor function, spinal cord tissue morphology, and the levels of Notch-related proteins and proinflammatory transcripts were compared between groups. To validate the hypothesis that the therapeutic effects of ADSCs are partly due to Notch1 signaling inhibition, a Jagged1 small interfering RNA (siRNA) was injected into the spinal cord to knock down Jagged1/Notch signaling. Neuronal staining and analyses of microglia/macrophage activation and signaling pathways were performed.
resultsWe demonstrated that ADSCs survived in the injured spinal cord for at least 28 days without differentiating into glial or neuronal elements. ADSC treatment resulted in significant downregulation of proinflammatory mediator expression and reduced ionized calcium-binding adapter molecule 1 (IBA1) and ED-1 staining in the injured spinal cord, eventually improving functional recovery. The augmentation of the Jagged1/Notch signaling pathway after SCI was suppressed by ADSC transplantation. The inhibition of the Jagged1/Notch signaling pathway by Jagged1 siRNA resulted in decreases in SCI-induced proinflammatory cytokines and the activation of microglia and an increase in the survival of neurons. Furthermore, Jagged1 knockdown suppressed the phosphorylation of JAK/STAT3 in astrocytes following SCI.
conclusionThe results of this study demonstrated that the therapeutic effects of ADSCs in SCI mice were partly due to Jagged1/Notch signaling pathway inhibition and a subsequent reduction in JAK/STAT3 phosphorylation in astrocytes.
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