纳米可导电支架搭载MMP-2/Notch1转染的嗅鞘细胞移植修复脊髓损伤的研究

Neurological function recovery after spinal cord injury has been a hot research and medical difficulty, cell transplantation has become an important means for the treatment of spinal cord injury. As the carrier of transplanted cells, cell scaffold material selection and preparation is very important,but no satisfactory scaffold has been found yet. We have found in preliminary work that conductive polymers in the electric field can promote cell migration and differentiation. The main subject of the item is to prepare conductive polymer nano-scale biodegradable scaffold poly [(glycine ethylester/aniline pentamer)phosphazene], which is combined with olfactory ensheathing cell transfected by plasmid MMP-2/Notch1 and transplanted into spinal cord hemisection injury model in rats.The influence of the scaffold on migration and differentiation of olfactory ensheathing cells in vitro and in vivo is to be observed, the recovery of neurological function in rats is to be evaluated through behavioral assessment, evoked potential, spinal cord pathological changes and ultrastructure after transplantation, and the mechanism of the composite transplantation for repairing spinal cord injury is to be explored.As a result,a new kind of safe and effective scaffold for cell transplantation may be foundIf the idea of this experiment can succeed and be used in clinical practice,the quality of life of patients with spinal cord injury will be significantly improved.

脊髓损伤后神经功能的恢复一直是医学界研究的热点和难点，细胞移植已成为治疗脊髓损伤的重要手段。作为移植细胞的载体，细胞支架材料的选择和制备十分重要，但目前仍未找到理想的细胞支架。我们在前期工作中发现可导电高分子材料在电场作用下能够促进细胞的迁移和分化，因此通过制备纳米级可降解导电高分子支架聚[(甘氨酸乙酯／苯胺五聚体)膦腈]，将其与MMP-2/Notch1质粒转染的嗅鞘细胞复合并联合移植于大鼠脊髓全切损伤模型，观察支架对嗅鞘细胞在体外、体内对嗅鞘细胞迁移和分化情况的影响，并通过对大鼠的行为学评定、诱发电位检测，大鼠脊髓组织的病理变化和超微结构的观察以评价复合物移植后大鼠神经功能的恢复情况，进一步探讨支架与嗅鞘细胞移植修复脊髓损伤的可能机制，以寻找一种新型的安全有效的细胞移植支架材料。如果这一实验思路获得成功并得以应用于临床实践，将会明显提高脊髓损伤患者的生活质量。

脊髓损伤后神经功能的恢复一直是医学界研究的热点和难点，细胞移植已成为治疗脊髓损伤的重要手段。作为移植细胞的载体，细胞支架材料的选择和制备十分重要，但目前仍未找到理想的细胞支架。本研究通过制备纳米级可降解导电高分子支架聚[(甘氨酸乙酯／苯胺五聚体)膦腈]（PGAP），将其与MMP-2/Notch1质粒转染的嗅鞘细胞复合并联合移植于大鼠脊髓全切损伤模型，观察支架对嗅鞘细胞在体外、体内对嗅鞘细胞迁移情况的影响，并通过对大鼠的行为学评定、大鼠脊髓组织的病理变化的观察以评价复合物移植后大鼠神经功能的恢复情况。研究结果显示制备的PGAP支架与大鼠嗅鞘细胞有良好的生物相容性，嗅鞘细胞能够在PGAP支架上存活、粘附和增殖。电刺激作用有助于支架上的嗅鞘细胞增殖和迁移。电刺激作用下PGAP支架与转染后的嗅鞘细胞复合物移植有助于大鼠损伤脊髓处轴突再生，进而有助于大鼠神经功能的恢复。我们认为PGAP支架可以作为嗅鞘细胞的良好载体用于治疗脊髓损伤，但这一研究有待于进一步深入，如果将来得以进一步应用于临床实践，将会明显提高脊髓损伤患者的生活质量。