Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Department of Neurology, Medical Center, Columbia University, New York City, NY 10032, USA.
Biomaterials. 2015 Jun;53:40-9. doi: 10.1016/j.biomaterials.2015.02.065. Epub 2015 Mar 9.
Human pluripotent stem cells (hPSCs) have the potential to differentiate along the retinal lineage. However, most induction systems are dependent on multiple small molecular compounds such as Dkk-1, Lefty-A, and retinoic acid. In the present study, we efficiently differentiated hPSCs into retinal cells using a retinal differentiation medium (RDM) without the use of small molecular compounds. This novel differentiation system recapitulates retinal morphogenesis in humans, i.e. hPSCs gradually differentiate into optic vesicle-shaped spheres, followed by optic cup-shaped spheres and, lastly, retinal progenitor cells. Furthermore, at different stages, hPSC-derived retinal cells mirror the transcription factor expression profiles seen in their counterparts during human embryogenesis. Most importantly, hinge epithelium was found between the hPSC-derived neural retina (NR) and retinal pigment epithelium (RPE). These data suggest that our culture system provides a new method for generating hPSC-derived retinal cells that, for the first time, might be used in human transplantation.
人多能干细胞(hPSCs)具有沿视网膜谱系分化的潜能。然而,大多数诱导系统依赖于多种小分子化合物,如 Dkk-1、Lefty-A 和视黄酸。在本研究中,我们使用不含小分子化合物的视网膜分化培养基(RDM)有效地将 hPSCs 分化为视网膜细胞。该新型分化系统再现了人类视网膜形态发生,即 hPSCs 逐渐分化为视囊状球体,然后是视杯状球体,最后是视网膜祖细胞。此外,在不同阶段,hPSC 衍生的视网膜细胞反映了其在人类胚胎发生过程中对应的转录因子表达谱。最重要的是,在 hPSC 衍生的神经视网膜(NR)和视网膜色素上皮(RPE)之间发现了铰链上皮。这些数据表明,我们的培养系统为生成 hPSC 衍生的视网膜细胞提供了一种新方法,这可能是首次用于人类移植。