Acute traumatic spinal cord injury is a devastating event without effective therapeutic approach. The feeble plasticity of spinal cord microvascular endothelial cells (SCMECs) after trauma is one of the major causes for the exacerbation of spinal cord injury. Therefore, improving the plasticity and regeneration of SCMECs is crucial to promote recovery after spinal cord injury. For the present study, we explored the influence of exosomes derived from neural stem cells (NSCs-Exos) on the spinal cord microvascular regeneration after spinal cord injury and determined the underlying mechanisms. After the primary NSCs and SCMECs were extracted, exosomes were isolated from NSCs conditioned medium and used to co-incubated with the SCMECs in vitro, and then the effect of exosomes on the angiogenic activities of SCMECs was measured. The candidate molecules involved in the NSCs-Exos-mediated angiogenesis were screened using Western blotting. The effect of NSCs-Exos on angiogenesis and spinal cord functional recovery after injury in vivo was analyzed. The results demonstrated that NSCs-Exos could enhance the angiogenic activities of SCMECs, and were highly enriched in VEGF-A. The level of VEGF-A was downregulated in NSCsshVEGF-A-Exos and the pro-angiogenic effects on cocultured SCMECs were inhibited. Furthermore, NSCs-Exos significantly accelerated the microvascular regeneration, reduced the spinal cord cavity, and improved the Basso mouse scale scores in spinal cord injury mice. This work provides the evidence of the underlying mechanism of NSCs-Exos-mediated angiogenesis and suggests a novel therapeutic target for spinal cord injury. Impact statement The feeble plasticity of SCMECs after trauma is one of the major causes for the exacerbation of SCI. Therefore, improving the regeneration ability of SCMECs is crucial to promote spinal cord functional recovery after injury. Our current study uncovered that NSCs-Exos could promote SCMECs migration, tube formation and proliferation in vitro, and further identified that exosomal VEGF-A mediated the pro-angiogenic effect. Furthermore, we observed a remarkable microvascular density increase, spinal cord cavity shrinkage, and motor function recovery in SCI mice treated with NSCs-Exos, which confirmed the therapeutic effects of NSCs-Exos to alleviate SCI. Downregulating VEGF-A partially abolished these effects of NSCs-Exos. This is the first study to reveal that NSCs-Exos has the pro-angiogenic effect on SCMECs by transferring VEGF-A and promote microvascular regeneration and tissue healing, indicating that NSCs-Exos can become a promising therapeutic bioagent for facilitating the functional recovery of SCI.
Our results suggest that PQQ can protect rat NP cells against oxidative stress via a mitochondria-mediated pathway. PQQ might be useful as a potential pharmaceutical agent in the prevention of intervertebral disc degeneration.
To develop adriamycin (ADM)-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles in a porous nano-hydroxyapatite/collagen scaffold (ADM-PLGA-NHAC). To provide novel strategies for future treatment of osteosarcoma, the properties of the scaffold, including its in vitro extended-release properties, the inhibition effects of ADM-PLGA-NHAC on the osteosarcoma MG63 cells, and its bone repair capacity, were investigated in vivo and in vitro. The PLGA copolymer was utilized as a drug carrier to deliver ADM-PLGA nanoparticles (ADM-PLGA-NP). Porous nano-hydroxyapatite and collagen were used to materials to produce the porous nano-hydroxyapatite/collagen scaffold (NHAC), into which the ADM-PLGA-NP was loaded. The performance of the drug-carrying scaffold was assessed using multiple techniques, including scanning electron microscopy and in vitro extended release. The antineoplastic activities of scaffold extracts on the human osteosarcoma MG63 cell line were evaluated in vitro using the cell counting kit-8 (CCK8) method and live-dead cell staining. The bone repair ability of the scaffold was assessed based on the establishment of a femoral condyle defect model in rabbits. ADM-PLGA-NHAC and NHAC were implanted into the rat muscle bag for immune response experiments. A tumor-bearing nude mice model was created, and the TUNEL and HE staining results were observed under optical microscopy to evaluate the antineoplastic activity and toxic side effects of the scaffold. The composite scaffold demonstrated extraordinary extended-release properties, and its extracts also exhibited significant inhibition of the growth of osteosarcoma MG63 cells. In the bone repair experiment, no significant difference was observed between ADM-PLGA-NHAC and NHAC by itself. In the immune response experiments, ADM-PLGA-NHAC exhibited remarkable biocompatibility. The in vivo antitumor experiment revealed that the implantation of ADM-PLGA-NHAC in the tumor resulted in a improved antineoplastic effect and fewer adverse side effects than direct intraperitoneal injection of ADM. The ADM-PLGA-NHAC developed in this study exhibited excellent extended-release drug properties, bone repairing and antineoplastic efficacy, which make it a promising osteoconductivity material with the capability to inhibit osteosarcoma.
Background: In spinal cord injury (SCI), systemic inflammation and the death of nerve cells in the spinal cord are life threatening. The connection between gut microbiota and signaling pathways has been a hot research topic in recent years. The Toll-like receptor 4/Myeloid differentiation factor 88 (TLR4/MyD88) signaling pathway is closely related to the inflammatory response. This study explored whether the gut microbiota imbalance could affect the TLR4/MyD88 signaling pathway to regulate SCI to provide a new basis for SCI research and treatment.Methods: An SCI model was constructed to study the influence on the injury of gut microbiota. 16S amplicon sequencing was used to identify the diversity and abundance of gut microbes. Fecal microbiota transplantation was performed in mice with SCI. ELISA was used to detect the serum levels of pro-inflammatory and anti-inflammatory factors in mice. Hematoxylin and eosin staining was used to observe SCI in mice. Immunofluorescence was used to detect the rates of loss glial fibrillary acidic protein (GFAP), neuronal nuclear protein (NeuN), and ionized calcium-binding adapter molecule 1 (IBA1) in the spinal cord as indicators of apoptosis. The expression of the TLR4/MyD88 signaling pathway was detected by qRT-PCR and western blotting.Results: Significant differences were observed in the gut microbiota of SCI mice and normal mice. The gut microbiota of SCI mice was imbalanced. The levels of pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in SCI mice were increased, as was the level of the toxic induced nitric oxide synthase. The levels of anti-inflammatory factors IL-4, transforming growth factor-β, and IL-10 were decreased, as was the level of arginase-1. The apoptosis rates of GFAP, NeuN, and IBA1 were increased. The TLR4/MyD88 signaling pathway was activated. In the SCI group, inflammation increased after fecal transplantation, apoptosis of GFAP, NeuN, and IBA1 increased, and SCI was more serious.Conclusion: The TLR4/MyD88 signaling pathway promotes the death of nerve cells by inducing inflammation. Gut microbiota dysregulation can lead to aggravated SCI by activating the TLR4/MyD88 signaling pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.