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

Xiufeng Zhong, Christian Gutierrez, Tian Xue, Christopher Hampton, M. Natalia Vergara, Li-Hui Cao, Ann Peters, Tea Soon Park, Elias T. Zambidis, Jason S. Meyer, David M. Gamm, King-Wai Yau and M. Valeria Canto-Soler ()
Additional contact information
Xiufeng Zhong: Wilmer Eye Institute, Johns Hopkins University School of Medicine
Christian Gutierrez: Wilmer Eye Institute, Johns Hopkins University School of Medicine
Tian Xue: School of Life Sciences and Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China
Christopher Hampton: Wilmer Eye Institute, Johns Hopkins University School of Medicine
M. Natalia Vergara: Wilmer Eye Institute, Johns Hopkins University School of Medicine
Li-Hui Cao: Johns Hopkins University School of Medicine
Ann Peters: Institute for Cell Engineering and Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine
Tea Soon Park: Institute for Cell Engineering and Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine
Elias T. Zambidis: Institute for Cell Engineering and Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine
Jason S. Meyer: and Stark Neuroscience Research Institute, Indiana University–Purdue University
David M. Gamm: McPherson Eye Research Institute and Waisman Center Stem Cell Research Program, University of Wisconsin
King-Wai Yau: Wilmer Eye Institute, Johns Hopkins University School of Medicine
M. Valeria Canto-Soler: Wilmer Eye Institute, Johns Hopkins University School of Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5047

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