Nemati S Hiva, Seiedrazizadeh Zahra, Simorgh Susan, Hesaraki Mahdi, Kiani Sahar, Javan Mohammad, Pakdel Farzad, Satarian Leila
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Cell J. 2022 Mar;24(3):120-126. doi: 10.22074/cellj.2022.7873.
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.
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.
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.
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.
视神经的任何损伤都可能导致不可再生轴突的退化，并最终导致视网膜神经节细胞（RGCs）死亡，在大多数情况下，手术或药物无法治愈。在许多研究中，已经评估了不同类型干细胞在神经系统中的神经保护功能，这些研究探讨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（NPCs）分泌多种对视觉系统保护至关重要的营养因子。我们旨在评估NPCs在视神经挤压（ONC）小鼠模型中的治疗潜力。
在本实验研究中，使用头蛋白和视黄酸从人胚胎干细胞（hESCs）中产生NPCs。50只小鼠被分为以下三组：i. 完整组，ii. 载体组[视神经挤压+汉克平衡盐溶液（HBSS）]，iii. 治疗组（视神经挤压+NPCs）。使用视觉悬崖试验检查小鼠的视觉行为，并通过Brn3a免疫染色和使用DiI注射的逆行追踪来评估RGCs数量。
通过视觉悬崖静脉注射50,000个NPCs并未产生任何视觉改善。然而，我们的数据表明，通过Brn3a染色和逆行追踪检查，与载体组相比，NPCs对RGCs的保护作用高出两倍以上。
我们的研究表明，静脉注射NPCs可能通过营养因子介导保护RGCs。由于这种能力以及良好生产规范（GMP）级生产的可行性，NPCs可用于视神经保护。
