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Lookup NU author(s): Majed Felemban, Dr Birthe HilgenORCiD, Dr Darin Zerti, Dr Nicola Hunt, Dr Dean Hallam, Dr Kathryn White, Dr Yuchun Ding, Professor Natalio KrasnogorORCiD, 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).
Tissue specific extracellular matrices (ECM) provide structural support and enable access to molecular signals and metabolites which are essential for directing stem cell renewal and differentiation. To mimic this phenomenon in vitro, tissue decellularisation approaches have been developed, resulting in the generation of natural ECM scaffolds that have comparable physical and biochemical properties of the natural tissues and are currently gaining traction in tissue engineering and regenerative therapies due to the ease of standardized production, and constant availability. In this manuscript we report the successful generation of decellularised ECM-derived peptides from neural retina (decel NR) and retinal pigment epithelium (decel RPE), and their impact on differentiation of human pluripotent stem cells (hPSCs) to retinal organoids. We show that culture media supplementation with decel RPE and RPE-conditioned media (CM RPE) significantly increases the generation of rod photoreceptors, whilst addition of decel NR and decel RPE significantly enhances ribbon synapse marker expression and the light responsiveness of retinal organoids. Photoreceptor maturation, formation of correct synapses between retinal cells and recording of robust light responses from hPSC-derived retinal organoids remain unresolved challenges for the field of regenerative medicine. Enhanced rod photoreceptor differentiation, synaptogenesis and light response in response to addition of decellularised matrices from RPE and neural retina as shown herein provide a novel and substantial advance in generation of retinal organoids for drug screening, tissue engineering and regenerative medicine.
Author(s): Dorgau B, Felemban M, Hilgen G, Kienning N, Zert D, Hunt N, Doherty M, Whifield P, Hallam D, White K, Ding Y, Krasnogor N, Alaama J, Asfour HZ, Sernagor E, Lako M
Publication type: Article
Publication status: Published
Journal: Biomaterials
Year: 2019
Volume: 199
Pages: 63-75
Print publication date: 01/04/2019
Online publication date: 22/01/2019
Acceptance date: 20/01/2019
Date deposited: 21/01/2019
ISSN (print): 0142-9612
ISSN (electronic): 1878-5905
Publisher: Elsevier BV
URL: https://doi.org/10.1016/j.biomaterials.2019.01.028
DOI: 10.1016/j.biomaterials.2019.01.028
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