Kong Weijian, Qi Zhiping, Xia Peng, Chang Yuxin, Li Hongru, Qu Yunpeng, Pan Su, Yang Xiaoyu
Department of Orthopedic Surgery, The Second Hospital of Jilin University Ziqiang Street No. 218 Changchun Jilin 130041 PR China
Department of Cardiovascular Medicine, The Second Hospital of Jilin University Ziqiang Street No. 218 Changchun Jilin 130041 PR China.
RSC Adv. 2019 Jun 5;9(31):17801-17811. doi: 10.1039/c9ra01717h. eCollection 2019 Jun 4.
Spinal cord injury (SCI) is a common issue in the clinic that causes severe motor and sensory dysfunction below the lesion level. FTY720, also known as fingolimod, has recently been reported to exert a positive effect on the recovery from a spinal cord injury. Through local delivery to the lesion site, FTY720 effectively integrates with biomaterials, and the systemic adverse effects are alleviated. However, the effects of the proper mass ratio of FTY720 in biomaterials on neural stem cell (NSC) proliferation and differentiation, as well as functional recovery after SCI, have not been thoroughly investigated. In our study, we fabricated electrospun poly (lactide--glycolide) (PLGA)/FTY720 scaffolds at different mass ratios (0.1%, 1%, and 10%) and characterized these scaffolds. The effects of electrospun PLGA/FTY720 scaffolds on NSC proliferation and differentiation were measured. Then, a rat model of spinal transection was established to investigate the effects of PLGA/FTY720 scaffolds loaded with NSCs. Notably, 1% PLGA/FTY720 scaffolds exerted the best effects on the proliferation and differentiation of NSCs and 10% PLGA/FTY720 was cytotoxic to NSCs. Based on the Basso, Beattie, and Bresnahan (BBB) score, HE staining and immunofluorescence staining, the PLGA/FTY720 scaffold loaded with NSCs effectively promoted the recovery of spinal cord function. Thus, FTY720 properly integrated with electrospun PLGA scaffolds, and electrospun PLGA/FTY720 scaffolds loaded with NSCs may have potential applications for SCI as a nerve implant.
脊髓损伤（SCI）是临床上常见的问题，会导致损伤平面以下出现严重的运动和感觉功能障碍。FTY720，也被称为芬戈莫德，最近有报道称其对脊髓损伤的恢复有积极作用。通过局部递送至损伤部位，FTY720能有效地与生物材料结合，并减轻全身不良反应。然而，FTY720在生物材料中的合适质量比 对神经干细胞（NSC）增殖和分化以及SCI后功能恢复的影响尚未得到充分研究。在我们的研究中，我们制备了不同质量比（0.1%、1%和10%）的电纺聚（丙交酯-乙交酯）（PLGA）/FTY720支架，并对这些支架进行了表征。测量了电纺PLGA/FTY720支架对NSC增殖和分化的影响。然后，建立大鼠脊髓横断模型，研究负载NSC的PLGA/FTY720支架的作用。值得注意的是，1%的PLGA/FTY720支架对NSC的增殖和分化效果最佳，而10%的PLGA/FTY720对NSC具有细胞毒性。基于Basso、Beattie和Bresnahan（BBB）评分、苏木精-伊红（HE）染色和免疫荧光染色，负载NSC的PLGA/FTY720支架有效地促进了脊髓功能的恢复。因此，FTY720与电纺PLGA支架能很好地结合，负载NSC的电纺PLGA/FTY720支架作为神经植入物在SCI治疗中可能具有潜在应用价值。
