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.

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。