@article{ef9ddd49c87740fbbb8dd4efd146e889,
title = "Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs",
abstract = "Many forms of blindness result from the dysfunction or loss of retinal photoreceptors. Induced pluripotent stem cells (iPSCs) hold great potential for the modelling of these diseases or as potential therapeutic agents. However, to fulfill this promise, a remaining challenge is to induce human iPSC to recreate in vitro key structural and functional features of the native retina, in particular the presence of photoreceptors with outer-segment discs and light sensitivity. Here we report that hiPSC can, in a highly autonomous manner, recapitulate spatiotemporally each of the main steps of retinal development observed in vivo and form three-dimensional retinal cups that contain all major retinal cell types arranged in their proper layers. Moreover, the photoreceptors in our hiPSC-derived retinal tissue achieve advanced maturation, showing the beginning of outer-segment disc formation and photosensitivity. This success brings us one step closer to the anticipated use of hiPSC for disease modelling and open possibilities for future therapies.",
author = "Xiufeng Zhong and Christian Gutierrez and Tian Xue and Christopher Hampton and Vergara, {M. Natalia} and Cao, {Li Hui} and Ann Peters and Park, {Tea Soon} and Zambidis, {Elias T.} and Meyer, {Jason S.} and Gamm, {David M.} and Yau, {King Wai} and Canto-Soler, {M. Valeria}",
note = "Funding Information: We thank Dr Hai-Quan Mao and Xingyu Liu for help in establishing hiPSC cultures in the lab; Kyle Wallace and Amelia Verhoeven for training on the initial differentiation protocol; Dr Gerard Lutty and Rhonda Grebe for assistance with transmission electron microscopy; Drs Alexander M. Dizhoor, Robert S. Molday, David Hicks, Stephen Tsang and Jeremy Nathans for providing antibodies; Ruikang Liu, Jennica Kahkejian, Linus Amarikwa and Fuhua Peng for technical assistance, and all the members of the Canto-Soler{\textquoteright}s lab for contributions to techniques and discussions. This work was supported by grants to M.V.C.S. from the Maryland Stem Cell Research Fund (MSCRF; 2009-MSCRFE-0120-00 and 2012-MSCRFE-0207-00), The William and Ella Owens Medical Research Foundation, The J. Willard and Alice S. Marriott Foundation, the William & Mary Greve Special Scholar Award from Research to Prevent Blindness and NIH (EY022631), a generous gift from Mr. Michael B. Panitch, and by a CORE Grant to Wilmer Eye Institute (EY1765). T.X. was supported by the National Basic Research Program (973 Program) from the Ministry of Science and Technology of China (2013CB967700). E.T.Z was supported by grants from NIH/NHLBI (U01HL099775) and MSCRF (2011-MSCRF-II-0008-00; 2007-MSCRF-II-0379-00). J.S.M. was supported by BrightFocus Foundation (grant G2012027) and Fight for Sight. D.G. was supported by NIH grant R01EY021218 and the Foundation Fighting Blindness Wynn-Gund Translational Research Acceleration Award. K.W.Y was supported by NIH grant R01EY06837 and the Ant{\'o}nio Champalimaud Vision Award (Lisbon, Portugal).",
year = "2014",
month = jun,
day = "10",
doi = "10.1038/ncomms5047",
language = "English (US)",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}