ArticleStem cell reviews and reports2022
MSC secreted extracellular vesicles carrying TGF-beta upregulate Smad 6 expression and promote the regrowth of neurons in spinal cord injured rats.
Article in Stem cell reviews and reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Repair of spinal cord injury by bone marrow mesenchymal stem cell-derived exosomes: a systematic review and meta-analysis based on rat models.Frontiers in molecular neuroscience · 2024Pooled it
- An engineered exosome-based platform for targeted delivery to endogenous neural stem cells and fate modulation after spinal cord injury.Materials today. Bio · 2026Article
- Surface N-Glycosylation Dictates MSC-EV Uptake and CCR2-Driven Monocyte Recruitment to Inflamed Endothelium Under Shear Flow.Journal of extracellular vesicles · 2026Article
- Mesenchymal Stem/Stromal Cell-Free Therapies: Challenges and Opportunities.Molecular biotechnology · 2026Review
- In-Solution Characterization of Extracellular Vesicles: A New Approach to Evaluating Antibody Binding and Surface Interactions.Journal of extracellular vesicles · 2026Article
- MiR-124 Delivered by Extracellular Vesicles from Mesenchymal Stem Cell Exerts Neuroprotective Effects by Stabilizing the p62-Keap1-Nrf2 Pathway after Spinal Cord Injury in Rats.Molecular neurobiology · 2025Article
- Equine bone marrow MSC-derived extracellular vesicles mitigate the inflammatory effects of interleukin-1β on navicular tissues in vitro.Equine veterinary journal · 2025Article
- Mesenchymal Stem Cell-Derived Extracellular Vesicles in Alzheimer's Disease: A Novel Cell-Free Therapeutic Strategy and Diagnostic Biomarker.International journal of nanomedicine · 2025Review
- Mesenchymal Stem Cell-Induced Neuroprotection in Pediatric Neurological Diseases: Recent Update of Underlying Mechanisms and Clinical Utility.Applied biochemistry and biotechnology · 2024Review
- The Role of Exosomes from Mesenchymal Stem Cells in Spinal Cord Injury: A Systematic Review.International journal of stem cells · 2024Review
- Understanding molecular characteristics of extracellular vesicles derived from different types of mesenchymal stem cells for therapeutic translation.Extracellular vesicle · 2024Article
- Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration.International journal of molecular sciences · 2024Review
- Transplantation of Neural Stem Cells Loaded in an IGF-1 Bioactive Supramolecular Nanofiber Hydrogel for the Effective Treatment of Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Astroglial Cells: Emerging Therapeutic Targets in the Management of Traumatic Brain Injury.Cells · 2024Review
- Hitting the target: cell signaling pathways modulation by extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2024Review
- Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE.Frontiers in immunology · 2024Review
- Extracellular Vesicles: Therapeutic Potential in Central Nervous System Trauma by Regulating Cell Death.Molecular neurobiology · 2023Review
- Mesenchymal stem cell-derived extracellular vesicles therapy in traumatic central nervous system diseases: a systematic review and meta-analysis.Neural regeneration research · 2023Article
- Inflammation Modifies miR-21 Expression Within Neuronal Extracellular Vesicles to Regulate Remyelination Following Spinal Cord Injury.Stem cell reviews and reports · 2023Article
- Inflammatory stimulation of astrocytes affects the expression of miRNA-22-3p within NSCs-EVs regulating remyelination by targeting KDM3A.Stem cell research & therapy · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mesenchymal stem cells (MSCs) constitute a promising therapy for spinal cord injury (SCI) because they can provide a favorable environment for the regrowth of neurons by inhibiting receptor-regulated Smads (R-Smads) expression in endogenous neural stem cells (NSCs). However, their mechanism of action and effect on the expression of inhibitory Smads (I-Smads) remain unclear. Herein, we demonstrated that extracellular vesicles (EVs) from MSCs were able to upregulate the Smad 6 expression by carrying TGF-β, and the Smad 6 knockdown in NSCs partially weakened the bone marrow MSC (BMSC)-EV-induced effect on neural differentiation. We found that the expression of Smad 6 did not reduced owing to the TGF-β type I receptor kinase inhibitor, SB 431,542, treatment in the acute phase of injury in rats with SCI, thereby indicating that the Smad 6 expression was not only mediated by TGF-β, but also by the inflammatory factors and bone morphogenetic proteins (BMPs) as well. However, in the later phase of SCI, the Smad 6 expression decreased by the addition of SB 431,542, suggesting that TGF-β plays a key role in the mediation of Smad 6 expression in this phase. In addition, immunohistochemistry staining; hematoxylin-eosin staining; and the Basso, Beattie, and Bresnahan (BBB) scores revealed that the early inhibition of TGF-β did not increase neuron regrowth. However, this inhibition increased the cavity and the caspase-3 expression at 24 h post-injury, leading to a worse functional outcome. Conversely, the later treatment with the TGF-β inhibitor promoted the regrowth of neurons around the cavity, resulting in a better neurological outcome. Together, these results indicate that Smad 6 acts as a feedback regulator to prevent the over-differentiation of NSCs to astrocytes and that BMSC-EVs can upregulate Smad 6 expression by carrying TGF-β.
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