Intrathecal injection of autologous macrophages genetically modified to secrete BDNF by ex vivo electroporation improves hind limbs motor function after thoracic spinal cord injury in rats

通过离体电穿孔鞘内注射转基因分泌 BDNF 的自体巨噬细胞可改善大鼠胸脊髓损伤后的后肢运动功能

• 批准号: 23592168
• 负责人: OGATA Tadanori
• 金额: $ 3.33万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592168/
• 关键词: Spinal cord injury; rat; macrophage; gene therapy; BDNF; spinal cord

In order to develop an effective substance-delivery system for the treatment of spinal cord injury, we tried to overexpress BDNF protein in injury site by the transplantation of gene-modified autologous macrophages by lumbar puncture. Rat spinal cord injury was performed at the 11th thoracic vertebral level using a MASCIS impactor. Intrathecal injection of autologous macrophages genetically modified to secrete BDNF were injected into the subarachnoid space by lumbar puncture. Injected macrophages migrated and concentrated in the injured portion of the spinal cord and expressed GFP and BDNF proteins. The hind-limb function, evaluated by the BBB scale, in the BDNF-gene transferred animals, was significantly better than that in the vehicle animals from two weeks to eight weeks after the SCI. These results suggest that transplantation of gene-transfected autologous macrophages by lumbar puncture successfully improved hind-limb motor function via BDNF production after spinal cord injury.

为了开发一种有效的治疗脊髓损伤的物质传递系统，我们尝试通过腰椎穿刺移植基因修饰的自体巨噬细胞在损伤部位过量表达BDNF蛋白。使用MASCIS撞击器在第11胸椎水平进行大鼠脊髓损伤。通过腰椎穿刺将经基因修饰以分泌BDNF的自体巨噬细胞鞘内注射到蛛网膜下腔中。注射的巨噬细胞迁移并集中在脊髓的损伤部分，并表达GFP和BDNF蛋白。在脊髓损伤后2周至8周，通过BBB量表评估的BDNF基因转移动物的后肢功能显著优于载体动物。这些结果表明，通过腰椎穿刺移植基因转染的自体巨噬细胞成功地改善了脊髓损伤后通过BDNF产生的后肢运动功能。