Accelerated photoreceptor differentiation of hiPSC-derived retinal organoids by contact co-culture with retinal pigment epithelium
Accelerated photoreceptor differentiation of hiPSC-derived retinal organoids by contact co-culture with retinal pigment epithelium
复制标题
通过与视网膜色素上皮接触共培养加速 hiPSC 来源的视网膜类器官的光感受器分化
DOI：
10.1016/j.scr.2019.101491
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发表时间：
2019-08-01
影响因子：
1.2
通讯作者：
Xue, Tian
中科院分区：
文献类型：
--
作者：
Akhtar, Tasneem;Xie, Haohuan;Xue, Tian
来源于人类诱导的多能干细胞的视网膜有机体(ROS)重现了视网膜的三维结构，模拟了人类视网膜的发育，为临床前的视网膜移植提供了细胞来源。视网膜色素上皮(RPE)对正常的视网膜外生理至关重要，包括吞噬脱落的光感受器外节和分泌神经营养因子和血管营养生长因子。然而，ROS-RPE共培养能否在体外促进ROS中光感受器的分化仍是个未知数。本实验中，原代培养的小鼠RPE细胞与ROS在不同时间点接触共培养。我们的结果表明，RPE细胞促进了ROS中光感受器的分化，因为RPE和ROS之间的相互作用促进了不同分化阶段光感受器标志物的阶段特异性表达。因此，我们建立了一种基于人视网膜-RPE动力学模型的改进的共培养系统，用于评价眼科治疗。
Retinal organoids (ROs) derived from human-induced pluripotent stem cells recapitulate the three-dimensional structure of retina, mimic human retinal development, and provide cell sources for pre-clinical retinal transplantation. Retinal pigment epithelium (RPE) is crucial for normal outer retinal physiology, including phagocytosis of shed photoreceptor outer segments and secretion of neurotrophic and vasculotrophic growth factors. However, whether ROs-RPE co-culture can improve the differentiation of photoreceptors in ROs in vitro remains unknown. Herein, primary mouse RPE cells were contact co-cultured with ROs at different time points. Our results revealed that the RPE cells accelerated photoreceptor differentiation in ROs, as the cross talk between the RPE and ROs promoted the stage specific expression of photoreceptor markers at different differentiation stages. Thus, we established an improved co-culture system based on modeling of human retina-RPE dynamics during retinogenesis for the evaluation of ocular therapies.