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Nat Commun. 2014 Jun 10;5:4047. doi: 10.1038/ncomms5047.

Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs.

Author information

1
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
2
1] School of Life Sciences and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230026, China [2] Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
3
1] Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA [2].
4
Institute for Cell Engineering and Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, USA.
5
Department of Biology, Department of Medical and Molecular Genetics, and Stark Neuroscience Research Institute, Indiana University-Purdue University, Indianapolis, Indiana 46202, USA.
6
Department of Ophthalmology and Visual Sciences, McPherson Eye Research Institute and Waisman Center Stem Cell Research Program, University of Wisconsin, Madison, Wisconsin 53705, USA.
7
1] Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA [2] Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

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.

PMID:
24915161
PMCID:
PMC4370190
DOI:
10.1038/ncomms5047
[Indexed for MEDLINE]
Free PMC Article

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