Protection of visual functions by human neural progenitors in a rat model of retinal disease.
Protection of visual functions by human neural progenitors in a rat model of retinal disease.
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DOI：
10.1371/journal.pone.0000338
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发表时间：
2007-03-28
期刊：
影响因子：
3.7
通讯作者：
Lund, Raymond D.
中科院分区：
文献类型：
--
作者：
Gamm, David M.;Wang, Shaomei;Lu, Bin;Girman, Sergei;Holmes, Toby;Bischoff, Nicholas;Shearer, Rebecca L.;Sauve, Yves;Capowski, Elizabeth;Svendsen, Clive N.;Lund, Raymond D.
干细胞和祖细胞移植的一个有前途的临床应用是在退行性疾病的抢救治疗。这种策略试图通过利用这些多功能细胞通常显示的独特特性来保护而不是恢复宿主组织功能。在使用不同神经退行性疾病模型的研究中，移植的人神经祖细胞（hNPC）保护了大脑和脊髓内垂死的宿主神经元。基于这些报道，我们探索了hNPC移植在视网膜变性动物模型（皇家外科学院大鼠）中挽救视功能的潜力。在主要感光细胞丧失之前的年龄，动物接受单侧视网膜下注射hNPC或单独的培养基。主要结果采用视网膜电图、视力测量和上级丘的亮度阈值记录进行量化。在出生后90-100天，未处理的大鼠表现出很少或没有视网膜或视觉功能的时间点，hNPC处理的眼睛保留了大量的视网膜电活动和视野，具有接近正常的视敏度。当hNPC被基因工程化以分泌胶质细胞系源性神经营养因子时，功能功效进一步增强。生后150天组织学检查显示，hNPC在神经视网膜和视网膜色素上皮之间形成了一个几乎连续的色素层，并分布在视网膜内层。还观察到宿主视锥光感受器的伴随保存。在皇家外科学院大鼠视网膜下移植后，野生型和遗传修饰的人神经祖细胞存活时间延长，迁移广泛，分泌生长因子并挽救视觉功能。这些结果强调了hNPC在治疗视网膜变性疾病中的潜在治疗效用，并提示了其体内作用的潜在机制。
A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC) protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat. Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90–100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed. Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in vivo.
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影响因子：
1.8
作者：
Girman, S;Wang, S;Lund, RD
通讯作者：
Lund, RD
影响因子：
3.5
作者：
D'Cruz, PM;Yasumura, D;Vollrath, D
通讯作者：
Vollrath, D
影响因子：
4.2
作者：
Déglon, N;Tseng, JL;Aebischer, P
通讯作者：
Aebischer, P
影响因子：
4.8
作者：
Feng, W;Yasumura, D;Vollrath, D
通讯作者：
Vollrath, D
影响因子：
1.8
作者：
Girman, SV;Wang, S;Lund, RD
通讯作者：
Lund, RD