Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA, 17033, USA.
Mol Neurobiol. 2019 Sep;56(9):6056-6070. doi: 10.1007/s12035-019-1504-7. Epub 2019 Feb 4.
The ability of pluripotent stem cells (PSCs) to differentiate into retinal tissue has led to many attempts to direct this process to yield specific retinal cell types. The ability to do so would greatly impact both the study of normal retina development in model systems that can be precisely controlled and the generation of a homogeneous population of cells optimized for transplantation in cell replacement therapy. Thus far, many reviews have focused on the translational potential of PSC retinal studies. Here, we focus on the former by summarizing the advances and reflecting on the current limitations to using in vitro differentiation of PSCs into retinal cells and organoids to model in vivo retinal development, with a specific emphasis on photoreceptors. We discuss the versatility of PSC retinal differentiation systems in investigating specific developmental time points that are difficult to assess with classic developmental model systems as well as the potential for efficient screening of factors involved in regulating photoreceptor differentiation. PSCs can be used in conjunction with existing model systems to contribute to the understanding of retina and photoreceptor development, which in turn can enhance the success of using stem cells in translational studies.
多能干细胞 (PSCs) 分化为视网膜组织的能力促使人们尝试对这一过程进行定向，以产生特定的视网膜细胞类型。如果能够实现这一目标，将极大地影响到正常视网膜发育的研究，以及为细胞替代治疗中移植而优化的同质细胞群体的产生。迄今为止，许多综述都集中在 PSC 视网膜研究的转化潜力上。在这里，我们重点关注前者，总结了使用体外分化 PSCs 为视网膜细胞和类器官来模拟体内视网膜发育的进展和反思当前的局限性，特别强调了光感受器。我们讨论了 PSC 视网膜分化系统在研究特定发育时间点方面的多功能性，这些时间点很难用经典的发育模型系统进行评估，以及在调节光感受器分化的因素的有效筛选方面的潜力。可以将 PSCs 与现有的模型系统结合使用，以促进对视网膜和光感受器发育的理解，从而提高干细胞在转化研究中的应用成功率。
