Roles of PGS/PCL Scaffold in Promoting Differentiation of Human Embryonic Stem Cells Into Retinal Ganglion Cells

S. Behtaj, F. Karamali, Samaneh Najafian, E. Masaeli, M. N. Nasr Esfahani, M. Rybachuk
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Abstract

Stem cell-based therapeutic approaches have opened promising avenues to restoring vision in progressive optic neuropathies, including glaucomatous, and as such, the stem cell-based retinal ganglion cells (RGCs) replacement therapy offers a potential to replace degenerated RGCs and promote RGC axon regeneration. However, challenges associated with the successful generation of clinically safe and functional RGCs, which can appropriately integrate into the hosts’ retinas still remain unresolved. The use of polymeric tissue-supporting scaffolds is a known and tested solution to enhance the efficiency of cell delivery and differentiation process due to providing an appropriate physical environment and structural support, however, for RGC generation their application has been far from conclusive. Our study aims, firstly, to reveal a process that enables generation of RGCs from human embryonic stem cells (hESCs) that is simple, straightforward and repeatable and, secondly, to show the influence of the aligned poly(glycerol sebacate) (PGS)/poly(ε-caprolactone) (PCL) scaffold on this differentiation process. Our findings demonstrate that PGS/PCL scaffold promotes differentiation of hESCs into RGCs, possibly, by simulating cells active environmental signalling, as well as, by supporting the growth of RGCs neurites along their lengths.
PGS/PCL支架促进人胚胎干细胞向视网膜神经节细胞分化的作用
基于干细胞的治疗方法为包括青光眼在内的进行性视神经病变的视力恢复开辟了有希望的途径,因此,基于干细胞的视网膜神经节细胞(RGCs)替代疗法提供了替代退化的RGCs并促进RGCs轴突再生的潜力。然而,成功生成临床安全和功能性的RGCs,并将其适当地整合到宿主的视网膜中,所面临的挑战仍然没有解决。使用聚合物组织支撑支架是一种已知的和经过测试的解决方案,可以提高细胞传递和分化过程的效率,因为它提供了适当的物理环境和结构支持,然而,对于RGC的生成,它们的应用还远远没有定论。首先,我们的研究旨在揭示一种简单、直接和可重复的从人胚胎干细胞(hESCs)生成RGCs的过程,其次,显示排列的聚甘油癸二酸酯(PGS)/聚ε-己内酯(PCL)支架对这一分化过程的影响。我们的研究结果表明,PGS/PCL支架促进hESCs向RGCs分化,可能是通过模拟细胞活跃的环境信号,以及通过支持RGCs神经突沿其长度的生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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