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Protective effect of brain-derived neurotrophic factor and neurotrophin-3 overexpression by adipose-derived stem cells combined with silk fibroin/chitosan scaffold in spinal cord injury
Neurological Research ( IF 1.7 ) Pub Date : 2020-03-09 , DOI: 10.1080/01616412.2020.1735819
Wen-Chen Ji 1 , Meng Li 1 , Wan-Ting Jiang 2 , Xing Ma 1 , Jia Li 1
Affiliation  

Objectives: Spinal cord injury (SCI) is a most debilitating traumatic injury, and cytotherapy is a promising alternative treatment strategy. Here we investigated the effect and mechanism of adipose-derived stem/stromal cells (ASCs) with overexpressing brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) (BDNF-NT3) in combination with silk fibroin/chitosan scaffold (SFCS) in SCI.

Methods: Female Sprague-Dawley rats were used as an SCI model. SFCS,SFCS and ASCs, or ASCs overexpressing NT3, BDNF, and BDNF-NT3 were implanted into SCI rats. Basso, Beattie, and Bresnahan score, pathological changes, and spinal cord tissue and nerve fiber morphology were observed and assayed. GAP-43, GFAP, and caspase-3 expression was determined using immunohistochemistry and western blotting.

Results: Smoother spinal cords, less scar tissue, and lower inflammatory activity were found in the SFCS, SFCS and ASCs, ASCs with NT3, BDNF, and BDNF-NT3 overexpression treatment than in the untreated SCI rat groups. Increasing formation of nerve fibers was observed in the above groups in order. GAP-43 expression significantly increased, while GFAP and caspase-3 expression significantly decreased. These results indicated obvious alleviation in pathological changes and BDNF-NT3 overexpression in ASCs combined with SFCS treatment in SCI rats.

Conclusion: Thus, BDNF-NT3 overexpression from ASCs with SFCS had synergistic neuroprotective effects on SCI and may be a treatment option for SCI.



中文翻译:

脂肪干细胞联合丝素蛋白/壳聚糖支架对脑源性神经营养因子和neurotrophin-3过表达的保护作用

目的:脊髓损伤(SCI)是最使人衰弱的创伤,细胞疗法是一种有前途的替代治疗策略。在这里,我们研究了过度表达脑源性神经营养因子(BDNF)和神经营养蛋白3(NT3)(BDNF-NT3)与丝纤蛋白/壳聚糖支架(SFCS)结合的脂肪干/基质细胞(ASC)的作用和机制)。

方法:将雌性Sprague-Dawley大鼠用作SCI模型。将SFCS,SFCS和ASC或过表达NT3,BDNF和BDNF-NT3的ASC植入SCI大鼠。观察并分析了Basso,Beattie和Bresnahan评分,病理变化以及脊髓组织和神经纤维形态。使用免疫组织化学和蛋白质印迹确定GAP-43,GFAP和caspase-3的表达。

结果:与未治疗的SCI大鼠组相比,SFCS,SFCS和ASC,NT3,BDNF和BDNF-NT3过表达治疗的SFCS,SFCS和ASC,ASC的脊髓更平滑,疤痕组织更少,炎性活性更低。在上述各组中依次观察到神经纤维的形成增加。GAP-43表达显着增加,而GFAP和caspase-3表达显着降低。这些结果表明,在SCI大鼠中,ASCs联合SFCS治疗可明显减轻病理变化和BDNF-NT3过表达。

结论:因此,ASCs与SFCS的BDNF-NT3过表达对SCI具有协同的神经保护作用,可能是SCI的治疗选择。

更新日期:2020-04-20
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