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Effects of a combinatorial treatment with gene and cell therapy on retinal ganglion cell survival and axonal outgrowth after optic nerve injury.
Gene Therapy ( IF 5.1 ) Pub Date : 2019-06-26 , DOI: 10.1038/s41434-019-0089-0
Gabriel Nascimento-Dos-Santos 1 , Leandro Coelho Teixeira-Pinheiro 1 , Almir Jordão da Silva-Júnior 1 , Luiza Rachel Pinheiro de Carvalho 1 , Louise Alessandra Mesentier-Louro 1 , William W Hauswirth 2 , Rosalia Mendez-Otero 1 , Marcelo Felippe Santiago 1 , Hilda Petrs-Silva 1
Affiliation  

After an injury, axons in the central nervous system do not regenerate over large distances and permanently lose their connections to the brain. Two promising approaches to correct this condition are cell and gene therapies. In the present work, we evaluated the neuroprotective and neuroregenerative potential of pigment epithelium-derived factor (PEDF) gene therapy alone and combined with human mesenchymal stem cell (hMSC) therapy after optic nerve injury by analysis of retinal ganglion cell survival and axonal outgrowth. Overexpression of PEDF by intravitreal delivery of AAV2 vector significantly increased Tuj1-positive cells survival and modulated FGF-2, IL-1ß, Iba-1, and GFAP immunostaining in the ganglion cell layer (GCL) at 4 weeks after optic nerve crush, although it could not promote axonal outgrowth. The combination of AAV2.PEDF and hMSC therapy showed a higher number of Tuj1-positive cells and a pronounced axonal outgrowth than unimodal therapy after optic nerve crush. In summary, our results highlight a synergistic effect of combined gene and cell therapy relevant for future therapeutic interventions regarding optic nerve injury.

中文翻译:

基因和细胞疗法联合治疗对视神经损伤后视网膜神经节细胞存活和轴突生长的影响。

受伤后,中枢神经系统中的轴突不会长距离再生,并永久失去与大脑的连接。纠正这种状况的两种有前途的方法是细胞和基因疗法。在当前的工作中,我们通过分析视网膜神经节细胞的存活和轴突的生长,评估了色素上皮衍生因子(PEDF)基因疗法单独和与人间充质干细胞(hMSC)疗法联合治疗视神经损伤后的神经保护和神经再生潜力。通过玻璃体内递送AAV2载体过度表达PEDF可以显着增加Tuj1阳性细胞的存活率,并调节视神经挤压后4周神经节细胞层(GCL)中FGF-2,IL-1ß,Iba-1和GFAP免疫染色的调节。它不能促进轴突生长。AAV2的组合。PEDF和hMSC疗法比单模疗法在视神经压伤后显示出更高的Tuj1阳性细胞数量和明显的轴突生长。总而言之,我们的研究结果突出了基因和细胞联合治疗对未来视神经损伤治疗干预的协同作用。
更新日期:2019-11-18
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