人类胚胎干细胞衍生的神经祖细胞存活小鼠变性视神经轴突

Shiva Nemati, Zahra Seiedrazizadeh, Susan Simorgh, M. Hesaraki, S. Kiani, M. Javan, F. Pakdel, L. Satarian
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引用次数: 2

摘要

目的视神经的任何损伤都可能导致非再生轴突变性和视网膜神经节细胞(RGCs)的最终死亡,这在大多数情况下是无法通过手术或药物治愈的。不同类型的干细胞在神经系统中的神经保护功能已经在许多研究中被评估,这些研究调查了这些细胞在各种视网膜疾病模型中的有效性。神经祖细胞(npc)分泌各种各样的营养因子,对保护视觉系统至关重要。我们的目的是评估NPCs在ONC小鼠模型中的治疗潜力。材料与方法利用人胚胎干细胞(hESCs)中的头蛋白和维甲酸制备NPCs。50只小鼠分为以下三组:1 .完整组;载体[视神经挤压+汉克平衡盐溶液(HBSS)];治疗(视神经压迫+ npc)。采用视觉悬崖法检测小鼠视觉行为,采用Brn3a免疫染色法和DiI注射逆行示迹法评估小鼠RGC数量。结果经视觉悬崖静脉注射5万例npc无明显视觉改善。然而,我们的数据表明,通过Brn3a染色和逆行示踪检测,npc中rgc的保护作用是载药组的两倍以上。结论静脉注射NPCs对RGCs具有一定的保护作用,可能与营养因子有关。由于这种能力和良好生产规范(GMP)级生产的可行性,npc可用于视神经保护。
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Mouse Degenerating Optic Axons Survived by Human Embryonic Stem Cell-Derived Neural Progenitor Cells
Objective Any damage to the optic nerve can potentially lead to degeneration of non-regenerating axons and ultimately death of retinal ganglion cells (RGCs) that in most cases, are not curable by surgery or medication. Neuroprotective functions of different types of stem cells in the nervous system have been evaluated in many studies investigating the effectiveness of these cells in various retinal disease models. Neural progenitor cells (NPCs) secrete an assortment of trophic factors that are vital to the protection of the visual system. We aimed to assess the therapeutic potentials of NPCs in an ONC mouse model. Materials and Methods In this experimental study, NPCs were produced using noggin and retinoic acid from human embryonic stem cells (hESCs). Fifty mice were divided into the following three groups: i. Intact , ii. Vehicle [optic nerve crush+Hank’s balanced salt solution (HBSS)], and iii. Treatment (optic nerve crush+NPCs). The visual behavior of the mice was examined using the Visual Cliff test, and in terms of RGC numbers, they were assessed by Brn3a immunostaining and retrograde tracing using DiI injection. Results Intravenous injection of 50,000 NPCs through visual cliff did not produce any visual improvement. However, our data suggest that the RGCs protection was more than two-times in NPCs compared to the vehicle group as examined by Brn3a staining and retrograde tracing. Conclusion Our study indicated that intravenous injection of NPCs could protect RGCs probably mediated by trophic factors. Due to this ability and good manufacturing practices (GMP) grade production feasibility, NPCs may be used for optic nerve protection.
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