Kadkhodaeian Hamid Aboutaleb, Salati Amir, Ansari Mojtaba, Taghdiri Nooshabadi Vajihe
Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Department of Anatomical Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
Basic Clin Neurosci. 2021 Jul-Aug;12(4):523-532. doi: 10.32598/bcn.2021.12.4.2230.1. Epub 2021 Jul 1.
Retinal Pigment Epithelium (RPE) layer deterioration is a leading cause of Age-Related Macular Degeneration (AMD), i.e., the most significant reason for irreversible blindness. The present study aimed to track the Neurosphere-Derived (NS) from Bone Marrow Stromal Stem Cells (BMSCs) grafted into the sub-retinal space (destruction of the RPE layer by sodium iodate).
RPE degeneration model was performed using the injection of 5% sodium iodate performed in the retro-orbital sinus of Wistar rats. BMSCs were extracted from the examined rat femur and induced into NS, using EGF, bFGF, and B27. BrdU-NS labeled cells were transplanted into the sub-retinal space. For detecting BMSCs and NS markers, immunocytochemistry was performed. Moreover, immunohistochemical was conducted for tracking the transplanted cells in the RPE and sensory retina.
The immunocytochemistry of BMSCs cells displayed the expression of mesenchymal stem cells markers (CD90; 99%±1), CD166 (98%±2), CD44 (99%±1). Additionally, the expression of neural lineage markers in NS, such as SOX2, OCT4, Nanog, Nestin, and Neurofilaments (68, 160, 200) revealed the differentiation from BMSCs. Tracking BrdU-NS labeled suggested these aggregations in most layers of the retina.
Our study data indicated that BMSCs derived neurosphere had the potential to migrate in injured retinal and integrate into the neurosensory retina. These data can be useful in finding safe cells for replacement therapy in AMD.
视网膜色素上皮（RPE）层退化是年龄相关性黄斑变性（AMD）的主要原因，即不可逆失明的最重要原因。本研究旨在追踪移植到视网膜下间隙（通过碘酸钠破坏RPE层）的骨髓基质干细胞（BMSCs）来源的神经球（NS）。
使用向Wistar大鼠眶后窦注射5%碘酸钠建立RPE退化模型。从受试大鼠股骨中提取BMSCs，并使用表皮生长因子（EGF）、碱性成纤维细胞生长因子（bFGF）和B27诱导其成为神经球。将用5-溴脱氧尿嘧啶核苷（BrdU）标记的神经球细胞移植到视网膜下间隙。通过免疫细胞化学检测BMSCs和神经球标志物。此外，进行免疫组织化学以追踪RPE和感觉视网膜中的移植细胞。
BMSCs细胞的免疫细胞化学显示间充质干细胞标志物（CD90；99%±1）、CD166（98%±2）、CD44（99%±1）的表达。此外，神经球中神经谱系标志物的表达，如性别决定区Y框蛋白2（SOX2）、八聚体结合转录因子4（OCT4）、 Nanog基因、巢蛋白和神经丝（68、160、200）显示了从BMSCs的分化。追踪用BrdU标记的神经球表明这些细胞聚集在视网膜的大多数层中。
我们的研究数据表明，BMSCs来源的神经球有潜力迁移至受损视网膜并整合到神经感觉视网膜中。这些数据有助于寻找用于AMD替代治疗的安全细胞。
