Grafts of fibroblasts genetically modified to secrete NGF, BDNF, NT-3, or basic FGF elicit differential responses in the adult spinal cord
Grafts of fibroblasts genetically modified to secrete NGF, BDNF, NT-3, or basic FGF elicit differential responses in the adult spinal cord
复制标题
DOI：
10.1016/0963-6897(95)02028-4
复制
发表时间：
1996-03-01
影响因子：
3.3
通讯作者：
Tuszynski, MH
中科院分区：
文献类型：
--
作者：
Nakahara, Y;Gage, FH;Tuszynski, MH
神经营养因子对发育中脊髓的神经元和轴突的反应已有较好的研究，但对成年大鼠脊髓对神经营养因子的反应知之甚少。我们通过基因修饰原代大鼠成纤维细胞产生神经生长因子(NGF)、脑源性神经营养因子(BDNF)、神经营养因子-3(NT-3)或碱性成纤维细胞生长因子(BFGF)，然后将这些分泌神经营养因子的细胞移植到成年大鼠的脊髓中央灰质中，移植前不进行脊髓损伤，2周至6个月后，背根源性感觉神经突起广泛穿透NGF-、NT-3-、而分泌BDNF的移植物没有引起生长反应，推测的去甲肾上腺素能神经突起也穿透了神经生长因子分泌细胞移植物，局部运动和皮质脊髓运动神经轴突没有穿透任何神经营养因子分泌的移植物。这些结果表明，未损伤或轻度受损的成人脊髓感觉和可能的去甲肾上腺素能群体保持着显著的神经营养因子反应，而运动神经突起即使在发育过程中表现出对那些神经营养因子的存活依赖，也相对抵抗。转基因细胞移植可以作为一种有用的工具来表征成年脊髓对神经营养因子的反应并设计促进损伤后轴突再生的策略。
Neuronal and axonal responses to neurotrophic factors in the developing spinal cord have been relatively well characterized, but little is known about adult spinal responses to neurotrophic factors, We genetically modified primary rat fibroblasts to produce either nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or basic fibroblast growth factor (bFGF), then grafted these neurotrophic factor-secreting cells into the central gray matter of the spinal cord in adult rats, Spinal cord lesions were not made prior to grafting, From 2 wk to 6 mo later, sensory neurites of dorsal root origin extensively penetrated NGF-, NT-3-, and bFGF-producing grafts, whereas BDNF-secreting grafts elicited no growth responses, Putative noradrenergic neurites also penetrated NGF-secreting cell grafts, Local motor and corticospinal motor axons did not penetrate any of the neurotrophic factor-secreting grafts, These results indicate that unlesioned or minimally lesioned adult spinal cord sensory and putative noradrenergic populations retain significant neurotrophic factor responsiveness, whereas motor neurites are comparatively resistant even to those neurotrophic factors to which they exhibit survival dependence during development, Grafts of genetically modified cells can be a useful tool for characterizing neurotrophic factor responsiveness in the adult spinal cord and designing strategies to promote axonal regeneration after injury.