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Decellularised extracellular matrix-derived peptides from neural retina and retinal pigment epithelium enhance the expression of synaptic markers and light responsiveness of human pluripotent stem cell derived retinal organoids

Lookup NU author(s): Majed Felemban, Dr Gerrit Hilgen, Dr Darin Zerti, Dr Nicola Hunt, Dr Dean Hallam, Dr Kathryn White, Dr Yuchun Ding, Professor Natalio Krasnogor, Professor Evelyne Sernagor, Professor Majlinda Lako

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

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.


Publication metadata

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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