Ji Wen-Chen, Li Meng, Jiang Wan-Ting, Ma Xing, Li Jia
Department of Orthopaedics, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Department of Ultrasound Diagnosis, The Fourth Hospital of Xi'an, Xi'an, China.
Neurol Res. 2020 May;42(5):361-371. doi: 10.1080/01616412.2020.1735819. Epub 2020 Mar 9.
: 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.: 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.: 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.: Thus, BDNF-NT3 overexpression from ASCs with SFCS had synergistic neuroprotective effects on SCI and may be a treatment option for SCI.
脊髓损伤(SCI)是一种极具致残性的创伤性损伤,而细胞疗法是一种有前景的替代治疗策略。在此,我们研究了过表达脑源性神经营养因子(BDNF)和神经营养因子-3(NT3)(BDNF-NT3)的脂肪来源干细胞/基质细胞(ASCs)与丝素蛋白/壳聚糖支架(SFCS)联合应用于脊髓损伤的效果及机制。
选用雌性Sprague-Dawley大鼠作为脊髓损伤模型。将SFCS、SFCS与ASCs、或过表达NT3、BDNF和BDNF-NT3的ASCs植入脊髓损伤大鼠体内。观察并测定Basso、Beattie和Bresnahan评分、病理变化以及脊髓组织和神经纤维形态。采用免疫组织化学和蛋白质印迹法测定生长相关蛋白43(GAP-43)、胶质纤维酸性蛋白(GFAP)和半胱天冬酶-3(caspase-3)的表达。
与未治疗的脊髓损伤大鼠组相比,SFCS组、SFCS与ASCs联合组、过表达NT3、BDNF和BDNF-NT3的ASCs治疗组的脊髓更光滑,瘢痕组织更少,炎症活性更低。上述各组依次观察到神经纤维形成增加。GAP-43表达显著增加,而GFAP和caspase-3表达显著降低。这些结果表明,ASCs联合SFCS治疗可明显减轻脊髓损伤大鼠的病理变化并使BDNF-NT3过表达。
因此,ASCs联合SFCS过表达BDNF-NT3对脊髓损伤具有协同神经保护作用,可能是脊髓损伤的一种治疗选择。