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Lookup NU author(s): Dr Carla Jackson, Dr Joseph Collin, Dr Rachel Queen, Dr Birthe HilgenORCiD, Dr Darin Zerti, Majed Felemban, Dr Kathryn White, Professor Evelyne SernagorORCiD, Professor Majlinda LakoORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
A major goal in the stem cell field is to generate tissues which can be utilised as a universal tool for in vitro models of development and disease, drug development, or as a resource for patients suffering from disease or injury. Great efforts are being made to differentiate human pluripotent stem cells in vitro towards retinal tissue, which is akin to native human retina in its cytoarchitecture and function, yet the numerous existing retinal induction protocols remain variable in their efficiency and do not routinely produce morphologically or functionally mature photoreceptors. Herein, we determine the impact thatthe method of embryoid body (EB) formation and maintenance as well as cell line background has on retinal organoid differentiation from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). Our data indicate that cell line specific differences dominate the variables that underline the differentiation efficiency in the early stages of differentiation. In contrast, the EB generation method and maintenance conditions determine the later differentiation and maturation of retinal organoids. Of the latter, the mechanical method of EB generation under static conditions, accompanied by media supplementation with Y27632 for the first 48 hours of differentiation, results in the most consistent formation of laminated retinal neuroepithelium containing mature and electrophysiologically responsive photoreceptors. Collectively our data provide substantive evidence for stage-specific differences in the ability to give rise to laminated retinae, which is determined by cell line specific differences in the early stages of differentiation and EB generation/maintenance methods at later stages.
Author(s): Mellough CB, Collin J, Queen R, Hilgen G, Dorgau B, Zerti D, Felemban M, White K, Sernagor E, Lako M
Publication type: Article
Publication status: Published
Journal: STEM CELLS Translational Medicine
Year: 2019
Volume: 8
Issue: 7
Pages: 694-706
Print publication date: 25/06/2019
Online publication date: 27/03/2019
Acceptance date: 11/02/2019
Date deposited: 12/02/2019
ISSN (print): 2157-6564
ISSN (electronic): 2157-6580
Publisher: Wiley
URL: https://doi.org/10.1002/sctm.18-0267
DOI: 10.1002/sctm.18-0267
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