Delivery of injectable thermo-sensitive hydrogel releasing nerve growth factor for spinal cord regeneration in rat animal model

Delivery of injectable thermo-sensitive hydrogel releasing nerve growth factor for spinal cord regeneration in rat animal model
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神经生长因子温敏凝胶注射剂促进大鼠脊髓再生的实验研究

DOI:
10.1016/j.jtv.2020.06.008
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发表时间:
2020-11-01
影响因子:
2.5
通讯作者:
Ostad, Seyed Nasser
Ostad, Seyed Nasser
中科院分区:
医学2区
文献类型:
--
作者:
Alizadeh, Akram;Moradi, Lida;Ostad, Seyed Nasser

文献摘要

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本研究的主要目的是探讨可注射chitosan/ll-glycerophosphate/hydroxyethylcellulose(CS/11-GP/HEC)水凝胶包裹的人脂肪间充质干细胞(HADSCs)过表达神经生长因子对脊髓再生的有利作用。制备了CS/11-GP/HEC水凝胶和伪慢病毒-NGF基因转导的hADSCs。用流变仪、扫描电子显微镜和四甲基偶氮唑盐比色法分别研究了水凝胶的力学性能、形态和细胞毒性。大鼠脊髓损伤后1周,用CS/ll-GP/HEC水凝胶转导hADSCs,并将转导hADSCs/CS/ll-GP/HEC水凝胶注入损伤部位。脊髓损伤动物和椎板切除非脊髓损伤动物分别为阴性对照组和假手术组。阳性对照组不接受手术干预。注射后8周,组织学检查显示转导hADSCs/CS/11-GP/HEC水凝胶组细胞增殖明显增强,脊髓损伤部位空洞缩小,运动功能增强(P
The main goal of this study was to explore the beneficial effect of nerve growth factor (NGF)-overexpressing of human adipose-derived mesenchymal stem cells (hADSCs) encapsulated in injectable chitosan/ll-glycerophosphate/hydroxyethylcellulose (CS/ll-GP/HEC) hydrogel for spinal cord regeneration. The CS/ll-GP/HEC hydrogel and genetically transduced hADSCs using pseudo-lentiviruses-NGF were prepared. The mechanical properties, morphology and cytotoxicity of the hydrogel were investigated by rheometry, scanning electron microscope (SEM), and MTT assay, respectively. Rats animals were undergone spinal cord injury (SCI), then one week post-injury, CS/ll-GP/HEC hydrogel, transduced hADSCs and transduced hADSCs/CS/ll-GP/HEC hydrogel injected into the site of the lesion. Animals with SCI and animals with laminectomy without SCI were considered as negative control and sham groups, respectively. Positive control group received no surgical intervention. At eight weeks post-injection, histological studies indicated a significant increase in cell proliferation, a smaller cavity in size at the SCI site as well as better locomotor functions for transduced hADSCs/CS/ll-GP/HEC hydrogel group (P