Gene therapy of Brain tumor using microglia as a carrier

我们研究了以分离的小胶质细胞为载体的动脉内基因导入系统。在新生小鼠中，从取自新生小鼠的混合胶质细胞培养物中分离的小胶质细胞在动脉内注射后保留了迁移到脑实质中的能力。在成年小鼠、大鼠和长爪沙鼠中，虽然有少量小胶质细胞迁移到脑实质内，但大部分仍滞留在脑毛细血管内。因此，我们停止使用这种传递系统，并决定使用腺病毒介导的基因转移系统，使用Cre-loxP系统。该系统包含星形胶质细胞特异性GFAP启动子和chymidine激酶基因，对培养的星形胶质细胞具有增殖抑制作用。目前利用C6胶质瘤进行基因治疗的实验正在进行中。

We examined the intraarterial gene delivery system into tumor brain using isolated microglia as a carrier. At new born mouse, microglia isolated from a mixed glial culture drawn from neonatal mice were retained the capability to migrate into the brain parenchyma after intra-arterial injection. Although a few microglia migrated into the brain parenchyma in adult mouse, rat and also Mongolian gerbil, almost of them were retained in the brain capillary. So we stopped the use of this delivery system, and decided the use of the adenovirus- mediated gene-transfer system using Cre-loxP system. This system was included astrocyte specific GFAP promoter and chymidine kinase gene, and showed the inhibitory effect of proliferation of cultured astrocyte. Now experiment of gene therapy using C6 glioma is on going.