生物材料支架激活内源性神经干细胞修复陈旧性脊髓损伤的机理研究

Repair of spinal cord injury in the adult mammalian is still an unresolved problem in the worldwide. For a long time, researches about SCI regeneration are mainly focused on the acute injury. Our recent researches demonstrated that implanting active biomaterial scaffold into T7-8 complete transverse defect of adult rats could active endogenous neural stem cells, raise and promote their migration to the injured area and then promote their proliferation, differentiate into mature neurons and integrate into neural circuit of the host, finally lead to partial sensorimotor functional recovery of rat hindlimb. Based on the previous study, the current object is planning to carry out the further study on the chronic SCI. We build the chronic SCI model in adult rat, combine the non-invasive imaging technique with the pathological method to identify the range of glial scar and cut the glial tissue. After then, we implant the bioactive material into the defect. All animals receive i.p. injection of BrdU after the operation. Combining the immunofluorescent staining, a planar multielectrode dish system, electrophysiology and behavioral detection and so on to observe the process and mechanism of endogenous neurogenesis induced by the biomaterial scaffold in the chronic SCI rat. These could provide the theoretical basis for the clinical restoration of chronic SCI and establish the technological foundation for clinical applications of biomaterial scaffold.

成年哺乳类脊髓损伤的修复是尚未解决的世界性难题。长期以来促进脊髓再生的相关研究主要集中在急性脊髓损伤。本团队前期发表的研究成果证明：将自主研发的活性生物材料支架移植至成年大鼠T7-8完全性切除5mm缺损中，生物材料支架可以向损伤局部持续释放神经营养素，激活内源性神经干细胞，募集其并迁移到损伤区、增殖并分化为成熟的神经元且整合到宿主的神经环路中，最终导致截瘫后肢部分功能恢复。本项目拟在前期研究的基础上进一步开展陈旧性脊髓损伤修复的研究，构建陈旧性脊髓损伤的动物模型，建立影像学无创鉴别陈旧性脊髓损伤胶质瘢痕范围的方法，结合病理学技术切除瘢痕组织后移植活性生物材料支架，术后腹腔注射BrdU并借助免疫荧光四标，平面微阵列技术，神经电生理技术，行为学评价等观察生物材料诱导陈旧性脊髓损伤后内源性神经发生的过程和机理，为生物材料支架应用于临床陈旧性脊髓损伤修复提供必要的理论依据并为临床应用奠定技术基础。

成年哺乳类脊髓损伤的修复是尚未解决的世界性难题。长期以来促进脊髓再生的相关研究主要集中在急性脊髓损伤。本团队前期发表的研究成果证明：将自主研发的活性生物材料支架移植至成年大鼠T7-8完全性切除5mm缺损中，生物材料支架可以向损伤局部持续释放神经营养素，激活内源性神经干细胞，募集其并迁移到损伤区、增殖并分化为成熟的神经元且整合到宿主的神经环路中，最终导致截瘫后肢部分功能恢复。本项目在前期研究的基础上开展了陈旧性脊髓损伤修复的研究，构建了大鼠及恒河猴陈旧性脊髓损伤模型，构建了无创鉴别胶质瘢痕范围的影像学方法，并完成了胶质瘢痕的切除。切除后，在损伤区移植了活性生物材料支架，神经电生理学、行为学及影像学结果均显示修复组的实验动物的功能得到改善。并且，使用免疫组化学等方法，阐明了生物材料诱导陈旧性脊髓损伤后内源性神经发生的过程和机理，为生物材料支架应用于临床陈旧性脊髓损伤修复提供乐必要的理论依据并为临床应用奠定基础。