Martínez-Serrano A, Fischer W, Björklund A
Department of Medical Cell Research, University of Lund, Sweden.
Neuron. 1995 Aug;15(2):473-84. doi: 10.1016/0896-6273(95)90051-9.
A highly NGF-secreting cell line was generated by retroviral transduction of a conditionally immortalized CNS-derived neural progenitor cell line. After transplantation to the nucleus basalis magnocellularis (NBM), the cells continue to express the NGF transgene for at least 10 weeks, producing sufficient NGF to reverse cholinergic neuron atrophy in aged rats and induce cellular hypertrophy in young rats. In cognitively impaired aged rats, transplants of the NGF-secreting cells placed either in the NBM and septum or in only the NBM induced a near-complete reversal of the spatial learning impairment. This was accompanied by a normalization of the size of the cholinergic neurons in the grafted areas. The results demonstrate that locally increased supply of NGF to the basal forebrain cholinergic nuclei has a significant impact on cognitive function and support the usefulness of neural progenitor cells for a long-term localized delivery of neurotrophins to the CNS.
通过逆转录病毒转导条件性永生化的中枢神经系统来源的神经祖细胞系，产生了一种高分泌神经生长因子（NGF）的细胞系。将这些细胞移植到基底大细胞核（NBM）后，它们至少持续10周表达NGF转基因，产生足够的NGF以逆转老年大鼠胆碱能神经元萎缩，并诱导年轻大鼠细胞肥大。在认知受损的老年大鼠中，将分泌NGF的细胞移植到NBM和隔区或仅移植到NBM，均可诱导空间学习障碍几乎完全逆转。这伴随着移植区域胆碱能神经元大小的正常化。结果表明，向基底前脑胆碱能核局部增加NGF供应对认知功能有显著影响，并支持神经祖细胞用于向中枢神经系统长期局部递送神经营养因子的有效性。
