Geraerts Martine, Eggermont Kristel, Hernandez-Acosta Pilar, Garcia-Verdugo Jose-Manuel, Baekelandt Veerle, Debyser Zeger
Laboratory for Molecular Virology and Gene Therapy, Katholieke Universiteit Leuven and IRC KULAK (Interdisciplinary Research Center, Katholieke Universiteit Leuven-Campus Kortrijk), Leuven, 3000, Belgium.
Hum Gene Ther. 2006 Jun;17(6):635-50. doi: 10.1089/hum.2006.17.635.
Modulation of adult neurogenesis may offer new therapeutic strategies for various brain disorders. In the adult mammalian brain the subventricular zone (SVZ) of the lateral ventricle is a region of continuous neurogenesis. Lentiviral vectors stably integrate into dividing and nondividing cells, in contrast to retroviral vectors, which integrate only into dividing cells. We compared their potential for gene transfer into both quiescent and slowly dividing stem cells as well as into more rapidly dividing progenitor cells. In contrast to retroviral vectors, stereotactic injection of lentiviral vectors into the SVZ of adult mice resulted in efficient and long-term marker gene expression in cells with characteristics of both immature type B cells and migrating precursor cells. After migration along the rostral migratory stream and differentiation, the number of enhanced green fluorescent protein (eGFP)-expressing granular and periglomerular interneurons increased over time in the ipsilateral olfactory bulb. Moreover, the number of eGFP-labeled neuronal progenitor cells in the SVZ increased over time. By intraventricular injection of lentiviral vectors we could restrict gene transfer to ependymal cells and type B astroglial-like stem cells. In conclusion, lentiviral vectors surpass retroviral vectors in efficient long-term in vivo marking of subventricular zone stem cells for basic research and therapeutic applications.
调节成体神经发生可能为各种脑部疾病提供新的治疗策略。在成年哺乳动物大脑中，侧脑室的室下区（SVZ）是一个持续发生神经发生的区域。与仅整合到分裂细胞中的逆转录病毒载体不同，慢病毒载体可稳定整合到分裂和非分裂细胞中。我们比较了它们将基因转移到静止和缓慢分裂的干细胞以及快速分裂的祖细胞中的潜力。与逆转录病毒载体不同，将慢病毒载体立体定向注射到成年小鼠的SVZ中，可在具有未成熟B型细胞和迁移前体细胞特征的细胞中实现高效且长期的标记基因表达。沿着吻侧迁移流迁移并分化后，同侧嗅球中表达增强型绿色荧光蛋白（eGFP）的颗粒状和球周中间神经元的数量随时间增加。此外，SVZ中eGFP标记的神经祖细胞数量也随时间增加。通过脑室内注射慢病毒载体，我们可以将基因转移限制在室管膜细胞和B型星形胶质样干细胞中。总之，在用于基础研究和治疗应用的室下区干细胞的高效长期体内标记方面，慢病毒载体优于逆转录病毒载体。
