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

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.




2018 ◽  
Vol 47 (1) ◽  
pp. 129-139 ◽  
Author(s):  
Guo-Jun Wei ◽  
Ke-wen Zheng ◽  
Gang An ◽  
Zuo-Wei Shi ◽  
Kai-Fu Wang ◽  
...  

Background/Aims: Transplantation of bone-marrow-derived mesenchymal stem cells (MSCs) promotes neural cell regeneration after spinal cord injury (SCI). Recently, we showed that suppression of microRNA-383 (miR-383) in MSCs increased the protein levels of glial cell line derived neurotrophic factor (GDNF), resulting in improved therapeutic effects on SCI. However, the overall effects of miR-383 suppression in MSCs on SCI therapy were not determined yet. Here, we addressed this question. Methods: We used bioinformatics tools to predict all miR-383-targeting genes, confirmed the functional bindings in a dual luciferase reporter assay. The effects of alteration of candidate genes in MSCs on cell proliferation were analyzed by MTT assay and by Western blotting for PCNA. The effects on angiogenesis were assessed by HUVEC assay. The effects on SCI in vivo were analyzed by transplantation of the modified MSCs into nude rats that underwent SCI. Results: Suppression of miR-383 in MSCs not only upregulated GDNF protein, but also increased vascular endothelial growth factor A (VEGF-A) and cyclin-dependent kinase 19 (CDK19), two other miR-383 targets. MiR-383-suppression-induced increases in CDK19 resulted in a slight but significant increase in MSC proliferation, while miR-383-suppression-induced increases in VEGF-A resulted in a slight but significant increase in MSC-mediated angiogenesis. Conclusions: Upregulation of CDK19 and VEGF-A by miR-383 suppression in MSCs further improve the therapeutic potential of MSCs in treating SCI in rats.



2017 ◽  
Vol 159 (5) ◽  
pp. 947-957 ◽  
Author(s):  
Dong Kwang Seo ◽  
Jeong Hoon Kim ◽  
Joongkee Min ◽  
Hyung Ho Yoon ◽  
Eun-Sil Shin ◽  
...  


2017 ◽  
Vol 40 (3) ◽  
pp. 609-615 ◽  
Author(s):  
Asrin Rahimi ◽  
Iraj Amiri ◽  
Amaneh Mohammadi Roushandeh ◽  
Zoleikha Golipour Choshali ◽  
Zohreh Alizadeh ◽  
...  


2021 ◽  
Vol 10 (5) ◽  
pp. 328-339
Author(s):  
Xufeng Jia ◽  
Guangping Huang ◽  
Shaohua Wang ◽  
Miao Long ◽  
Xiaojun Tang ◽  
...  

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.



2012 ◽  
Vol 8 (3) ◽  
pp. 953-962 ◽  
Author(s):  
Mevci Ozdemir ◽  
Ayhan Attar ◽  
Isinsu Kuzu ◽  
Murat Ayten ◽  
Enver Ozgencil ◽  
...  


2009 ◽  
Vol 18 (12) ◽  
pp. 1359-1368 ◽  
Author(s):  
Sung-Rae Cho ◽  
Yong Rae Kim ◽  
Hoi-Sung Kang ◽  
Sun Hee Yim ◽  
Chang-il Park ◽  
...  


2021 ◽  
Vol 18 ◽  
pp. 309-315
Author(s):  
Yijia Jia ◽  
Jianwen Yang ◽  
Tingsheng Lu ◽  
Xingwei Pu ◽  
Qiling Chen ◽  
...  




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