scholarly journals Extracellular vesicles derived from mesenchymal stem cells containing microRNA-381 protect against spinal cord injury in a rat model via the BRD4/WNT5A axis

2021 ◽  
Vol 10 (5) ◽  
pp. 328-339
Author(s):  
Xufeng Jia ◽  
Guangping Huang ◽  
Shaohua Wang ◽  
Miao Long ◽  
Xiaojun Tang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Luciferase Assay ◽  
Tunel Staining ◽  
Cord Injury ◽  
Neuron Apoptosis

Aims Non-coding microRNA (miRNA) in extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) may promote neuronal repair after spinal cord injury (SCI). In this paper we report on the effects of MSC-EV-microRNA-381 (miR-381) in a rodent model of SCI. Methods In the current study, the luciferase assay confirmed a binding site of bromodomain-containing protein 4 (BRD4) and Wnt family member 5A (WNT5A). Then we detected expression of miR-381, BRD4, and WNT5A in dorsal root ganglia (DRG) cells treated with MSC-isolated EVs and measured neuron apoptosis in culture by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. A rat model of SCI was established to detect the in vivo effect of miR-381 and MSC-EVs on SCI. Results We confirmed an interaction between miR-381 and BRD4, and showed that miR-381 overexpression inhibited the expression of BRD4 in DRG cells as well as the apoptosis of DRG cells through WNT5A via activation of Ras homologous A (RhoA)/Rho-kinase activity. Moreover, treatment of MSC-EVs rescued neuron apoptosis and promoted the recovery of SCI through inhibition of the BRD4/WNT5A axis. Conclusion Taken altogether, miR-381 derived from MSC-EVs can promote the recovery of SCI through BRD4/WNT5A axis, providing a new perspective on SCI treatment. Cite this article: Bone Joint Res 2021;10(5):328–339.

Enhanced axonal regeneration by transplanted Wnt3a-secreting human mesenchymal stem cells in a rat model of spinal cord injury

2017 ◽  
Vol 159 (5) ◽  
pp. 947-957 ◽  
Author(s):  
Dong Kwang Seo ◽  
Jeong Hoon Kim ◽  
Joongkee Min ◽  
Hyung Ho Yoon ◽  
Eun-Sil Shin ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Axonal Regeneration ◽  
Human Mesenchymal Stem Cells ◽  
Cord Injury

Sublethal concentration of H2O2 enhances the protective effect of mesenchymal stem cells in rat model of spinal cord injury

2017 ◽  
Vol 40 (3) ◽  
pp. 609-615 ◽  
Author(s):  
Asrin Rahimi ◽  
Iraj Amiri ◽  
Amaneh Mohammadi Roushandeh ◽  
Zoleikha Golipour Choshali ◽  
Zohreh Alizadeh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Protective Effect ◽  
Rat Model ◽  
Sublethal Concentration ◽  
Cord Injury

scholarly journals Effects of Magnetically Guided, SPIO-Labeled, and Neurotrophin-3 Gene-Modified Bone Mesenchymal Stem Cells in a Rat Model of Spinal Cord Injury

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Rui-Ping Zhang ◽  
Ling-Jie Wang ◽  
Sheng He ◽  
Jun Xie ◽  
Jian-Ding Li
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Therapeutic Effects ◽  
Magnetic Targeting ◽  
Bone Mesenchymal Stem Cells ◽  
Cord Injury

Despite advances in our understanding of spinal cord injury (SCI) mechanisms, there are still no effective treatment approaches to restore functionality. Although many studies have demonstrated that transplantingNT3gene-transfected bone marrow-derived mesenchymal stem cells (BMSCs) is an effective approach to treat SCI, the approach is often low efficient in the delivery of engrafted BMSCs to the site of injury. In this study, we investigated the therapeutic effects of magnetic targeting ofNT3gene-transfected BMSCs via lumbar puncture in a rat model of SCI. With the aid of a magnetic targeting cells delivery system, we can not only deliver the engrafted BMSCs to the site of injury more efficiently, but also perform cells imaging in vivo using MR. In addition, we also found that this composite strategy could significantly improve functional recovery and nerve regeneration compared to transplantingNT3gene-transfected BMSCs without magnetic targeting system. Our results suggest that this composite strategy could be promising for clinical applications.

scholarly journals Functional Recovery after the Transplantation of Neurally Differentiated Mesenchymal Stem Cells Derived from Bone Barrow in a Rat Model of Spinal Cord Injury

2009 ◽  
Vol 18 (12) ◽  
pp. 1359-1368 ◽  
Author(s):  
Sung-Rae Cho ◽  
Yong Rae Kim ◽  
Hoi-Sung Kang ◽  
Sun Hee Yim ◽  
Chang-il Park ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Functional Recovery ◽  
Rat Model ◽  
Cord Injury

scholarly journals Extracellular vesicles derived from CD73 modified human umbilical cord mesenchymal stem cells ameliorate inflammation after spinal cord injury

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiao Zhai ◽  
Kai Chen ◽  
Huan Yang ◽  
Bo Li ◽  
Tianjunke Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Inflammatory Cytokines ◽  
Human Umbilical Cord ◽  
M1 Polarization ◽  
Cord Injury

Abstract Background Spinal cord injury (SCI) is an inflammatory condition, and excessive adenosine triphosphate (ATP) is released into the extracellular space, which can be catabolized into adenosine by CD73. Extracellular vesicles have been designed as nano drug carriers in many diseases. However, their impacts on delivery of CD73 after SCI are not yet known. We aimed to construct CD73 modified extracellular vesicles and explore the anti-inflammatory effects after SCI. Methods CD73 engineered extracellular vesicles (CD73+ hucMSC-EVs) were firstly established, which were derived from human umbilical cord mesenchymal stem cells (hucMSCs) transduced by lentiviral vectors to upregulate the expression of CD73. Effects of CD73+ hucMSC-EVs on hydrolyzing ATP into adenosine were detected. The polarization of M2/M1 was verified by immunofluorescence. Furthermore, A2aR and A2bR inhibitors and A2bR knockdown cells were used to investigate the activated adenosine receptor. Biomarkers of microglia and levels of cAMP/PKA were also detected. Repetitively in vivo study, morphology staining, flow cytometry, cytokine analysis, and ELISA assay, were also applied for verifications. Results CD73+ hucMSC-EVs reduced concentration of ATP and promoted the level of adenosine. In vitro experiments, CD73+ hucMSC-EVs increased macrophages/microglia M2:M1 polarization, activated adenosine 2b receptor (A2bR), and then promoted cAMP/PKA signaling pathway. In mice using model of thoracic spinal cord contusion injury, CD73+ hucMSC-EVs improved the functional recovery after SCI through decreasing the content of ATP in cerebrospinal fluid and improving the polarization from M1 to M2 phenotype. Thus, the cascaded pro-inflammatory cytokines were downregulated, such as TNF-α, IL-1β, and IL-6, while the anti-inflammatory cytokines were upregulated, such as IL-10 and IL-4. Conclusions CD73+ hucMSC-EVs ameliorated inflammation after spinal cord injury by reducing extracellular ATP, promoting A2bR/cAMP/PKA pathway and M2/M1 polarization. CD73+ hucMSC-EVs might be promising nano drugs for clinical application in SCI therapy. Graphical Abstract

scholarly journals Intravenous Infusion of Mesenchymal Stem Cells Alters Motor Cortex Gene Expression in a Rat Model of Acute Spinal Cord Injury

2019 ◽  
Vol 36 (3) ◽  
pp. 411-420 ◽  
Author(s):  
Tsutomu Oshigiri ◽  
Toru Sasaki ◽  
Masanori Sasaki ◽  
Yuko Kataoka-Sasaki ◽  
Masahito Nakazaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Cortex ◽  
Rat Model ◽  
Intravenous Infusion ◽  
Acute Spinal Cord Injury ◽  
Cord Injury
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