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Biomaterials. 2019 Apr;199:63-75. doi: 10.1016/j.biomaterials.2019.01.028. Epub 2019 Jan 22.

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.

Author information

1
Institute of Genetic Medicine, Newcastle University, UK.
2
Institute of Neuroscience, Newcastle University, UK.
3
University of the Highlands and Islands, UK.
4
EM Research Services, Newcastle University, UK.
5
Interdisciplinary Computing and Complex Biosystems (ICOS) Research Group, Newcastle University, UK.
6
Department of Genetic Medicine and Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, Faculty of Medicine, King Abdulaziz University, Saudi Arabia.
7
Department of Medical Microbiology and Parasitology, Faculty of Medicine, Princess Al-Jawhara Center of Excellence in Research o Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
8
Institute of Genetic Medicine, Newcastle University, UK. Electronic address: majlinda.lako@ncl.ac.uk.

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 standardised 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.

KEYWORDS:

Decellularisation; Extracellular matrix; Human pluripotent stem cells; Neural retina; RPE; Retinal organoids

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