scholarly journals Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis

2020 ◽  
Author(s):  
Yong Cao ◽  
Xu Yan ◽  
Chunyuan Chen ◽  
Hui Xie ◽  
Hongbin Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Tube Formation ◽  
Akt Signaling Pathway ◽  
Functional Studies ◽  
Cord Injury

Abstract Background: Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate the effect of an administered injection of exosomes derived human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism.Methods: Exosome were isolate from USC and identified by transmission electron Microscopy (TEM) and western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model was assessed.Results: In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in (USC-Exo) and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway. Conclusion: Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

scholarly journals Local delivery of USC-derived exosomes harboring ANGPTL3 enhances spinal cord functional recovery after injury by promoting angiogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yong Cao ◽  
Yan Xu ◽  
Chunyuan Chen ◽  
Hui Xie ◽  
Hongbin Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Tube Formation ◽  
Akt Signaling Pathway ◽  
Functional Studies ◽  
Cord Injury

Abstract Background Spinal cord injury is a devastating clinical condition for which there are currently no effective therapeutic options. In the present study, we aim to investigate if the effect of an administered injection of exosomes derived from human urine stem cell (USC-Exo) embedded in hydrogel could improve the spinal cord functional recovery after injury and the underlying mechanism. Methods Exosomes were isolated from USC and identified by transmission electron microscopy (TEM) and Western blot. Functional assays in vitro were performed to assess the effects of USC-Exo on tube formation and migration, as well as their regulatory role in the PI3K/AKT signaling pathway activation. A locally administered injection of exosome embedded in hydrogel was used for SCI treatment. The effects of USC-Exo on functional recovery and the role of the candidate protein ANGPTL3 harboring in USC-Exo for promoting angiogenesis in SCI model were assessed. Results In the current study, we demonstrate that a locally administered injection of USC-Exo embedded in hydrogel can pass the spinal cord blood-brain barrier and deliver ANGPTL3 to the injured spinal cord region. In addition, the administration of human USC-Exo could enhance spinal cord neurological functional recovery by promoting angiogenesis. The results of mechanistic studies revealed that ANGPTL3 is enriched in USC-Exo and is required for their ability to promote angiogenesis. Functional studies further confirmed that the effects of USC-Exo on angiogenesis are mediated by the PI3K/AKT signaling pathway. Conclusion Collectively, our results indicate that USC-Exo serve as a crucial regulator of angiogenesis by delivering ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

scholarly journals Local delivery of USC-derived Exosome Carrying ANGPTL3 Enhance Spinal Cord Functional Recovery After Injury by Promoting Angiogenesis

2020 ◽  
Author(s):  
Xu Yan ◽  
Yong Cao ◽  
Chunyuan Chen ◽  
Hui Xie ◽  
Hongbin Lu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Umbilical Vein ◽  
Motor Evoked Potential ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Cord Injury

Abstract Background: Spinal cord injury (SCI) is a devastating clinical diseasewithout effectivetherapeuticapproach recently. In this study, we aim to investigate the effect of locally injection with exosome derived human urine stem cell (USC) embedding with hydrogelcould improve the spinal cord functional recovery after injury and the underlying mechanism.Methods:Exosome were isolate from USC andidentified by transmission electron microscopy and western blot. Functional assays using human umbilical vein endothelial cell (HUVEC) in vitro were performed to assess the effects of USC-Exosdeliverythe angiopoietin-like protein 3 (ANGPTL3) on tube formation and migration as well as their regulatory role in the PI3K/AKT signaling pathway activation. In vivo experiment we locally injection with exosome derived USC embedding with hydrogel for treatment of SCI. The effects of USC-Exos on functional recovery in spinal cord injury mice were tested by measuring motor evoked potential, histological and neovascular numbers. Meanwhile, the role of the candidate protein ANGPTL3 in USC-Exo for promoting angiogenesisin SCI was assessed.Results:In current study, we demonstrate that when given locallyinjection with exosomederivedhuman urine stem cell (USC) embeddingwith hydrogelcould pass the spinal cord blood brain barrier and delivery the angiopoietin-like protein 3 (ANGPTL3) to the injured spinal cord region. In addition, the administration of exosome derived from human USC could enhance spinal cord neurological functional recovery by promoting angiogenesis.The mechanism studies revealed that ANGPTL3 are enriched in USCexosome(USC-Exo) and required for USC exosome promoting angiogenesis. Functional studies further confirmed the effects caused by exosome derived from USC on angiogenesis wasmediated by PI3K/AKT signaling pathway. Conclusion:Collectively, our results indicated that USC derived exosome serve as a critical regulator of angiogenesis by transferring ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

scholarly journals Neural stem cell-derived exosomes facilitate spinal cord functional recovery after injury by promoting angiogenesis

2020 ◽  
Vol 245 (1) ◽  
pp. 54-65 ◽  
Author(s):  
Dong Zhong ◽  
Yong Cao ◽  
Cheng-Jun Li ◽  
Miao Li ◽  
Zi-Jie Rong ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Underlying Mechanism ◽  
Regeneration Ability ◽  
Therapeutic Effects ◽  
Cord Injury ◽  
Angiogenic Effect

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.

scholarly journals Photobiomodulation enhances facial nerve regeneration via activation of PI3K/Akt signaling pathway–mediated antioxidant response

2021 ◽  
Author(s):  
Bohan Li ◽  
Xiao Wang
Keyword(s):  
Facial Nerve ◽  
Signaling Pathway ◽  
Functional Recovery ◽  
Axonal Regeneration ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Effective Parameters ◽  
Neuroprotective Effects ◽  
Facial Nerves

AbstractFacial nerve dysfunction is a common clinical condition that leads to disfigurement and emotional distress in the affected individuals. This study aimed to evaluate whether photobiomodulation can enhance regeneration of crushed facial nerves and attempt to investigate the possible underlying mechanism of neuroprotective function and therapeutic target. Various parameters of photobiomodulation were assigned to the facial nerves and Schwann cells (SCs) separately during crushed injury in rats. Axonal regeneration, functional outcomes, and SC apoptosis, proliferation, and underlying mechanisms of action were evaluated by morphological, histopathological, and functional assessments, flow cytometry, western blotting, real-time PCR, and IncuCyte. The results showed that photobiomodulation improved axonal regeneration and functional recovery, and also promoted proliferation, and inhibited apoptosis of SCs, both of these were considered as the most effective parameters in 250mW group. In addition, the neuroprotective effects of photobiomodulation (500mW) were likely associated with oxidative stress–induced SC apoptosis via activation of the PI3K/Akt signaling pathway. Our results revealed that photobiomodulation significantly promoted axonal regeneration, functional recovery, and regeneration of the facial nucleus, and its mechanism was related to the up-regulation of the PI3K/Akt signaling pathway. These findings provide clear experimental evidence of photobiomodulation as an alternative therapeutic strategy for peripheral nerve damage.

Interference of interleukin-1β mediated by lentivirus promotes functional recovery of spinal cord contusion injury in rats via the PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Yi-li Wang ◽  
Xi Hu ◽  
Qin-xuan Li ◽  
Li-xin Zhang ◽  
Qing-jie Xia ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Signaling Pathway ◽  
Motor Function ◽  
Akt Signaling ◽  
Inflammatory Factors ◽  
Akt Signaling Pathway ◽  
Cord Injury ◽  
Spinal Cord Contusion ◽  
Recovery Of Motor Function

Abstract Background: Spinal cord contusion (SCC) results in a series of pathophysiologic consequences such as edema, apoptosis, and inflammation. However, inflammation may also be beneficial for the recovery of motor function after SCC, but the underlying mechanisms remain incompletely elucidated. Interleukin-1 beta (IL-1β) is a pro-inflammatory factor that has synergistic effects with other inflammatory factors to aggravate spinal cord injury. Inflammatory factors have been found to activate the serine/threonine-specific protein kinase, protein kinase B (AKT) and to inhibit cell survival, but it is not clear whether inflammation upregulates the expression of IL-1β in the rat model of SCC and subsequently interferes in the phosphatidylinositol-3-kinase (PI3K)/AKT signaling pathway. Therefore, this study explored whether IL-1β affects the recovery of motor function in spinal cord injury by interfering with the PI3K/AKT signaling pathway. Method: SCC rats were established by the Allen method. The Basso Beattie Bresnahan (BBB) scoring was used to assess motor function in the spinal cord of injured rats. Quantitative polymerase chain reaction and Western blot were used to determine the expression of genes and proteins of IL-1β, PI3K, and AKT1. Immunohistochemistry and immunofluorescence were used to locate and detect IL-1β and AKT1 proteins in spinal cord tissue. To further explore the underlying mechanism of IL-1β, lentivirus was constructed by RNA interfering (RNAi) technique to inhibit the expression of IL-1β, and bioinformatics was applied to show the relationship between IL-1β and AKT1. Results: BBB scores decreased after SCC, and IL-1β and AKT1 was located in the cytoplasm of spinal cord anterior horn neurons. In the early stage of SCC, the expression level of IL-1β gene and protein in the experimental group was higher than that in the sham operated group. At the same time, expression of the AKT1 gene decreased. After expression of IL-1β mediated by lentivirus was inhibited, BBB scores increased significantly, and spinal cord motor function improved. Bioinformatic analysis revealed a relationship between IL-1β and AKT1. In addition, AKT1 gene expression was upregulated and PI3K expression was unchanged in the PI3K/AKT signaling pathway. Conclusion IL-1β not only exacerbates the inflammatory response after SCC, but also interferes with motor function. Inhibition of IL-1β may promote recovery of spinal cord injury by upregulating AKT1 in the PI3K/AKT signaling pathway, which provides a new perspective for future clinical practice in treating spinal cord injury

Sign in / Sign up

Export Citation Format

Share Document