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Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF

The retinal pigmented epithelium (RPE) plays a critical role in photoreceptor survival and function. RPE deficits are implicated in a wide range of diseases that result in vision loss, including age-related macular degeneration (AMD) and Stargardt disease, affecting millions worldwide. Subretinal de...

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Autores principales: Al-Ani, Abdullah, Toms, Derek, Sunba, Saud, Giles, Kayla, Touahri, Yacine, Schuurmans, Carol, Ungrin, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583603/
https://www.ncbi.nlm.nih.gov/pubmed/34768747
http://dx.doi.org/10.3390/ijms222111317
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author Al-Ani, Abdullah
Toms, Derek
Sunba, Saud
Giles, Kayla
Touahri, Yacine
Schuurmans, Carol
Ungrin, Mark
author_facet Al-Ani, Abdullah
Toms, Derek
Sunba, Saud
Giles, Kayla
Touahri, Yacine
Schuurmans, Carol
Ungrin, Mark
author_sort Al-Ani, Abdullah
collection PubMed
description The retinal pigmented epithelium (RPE) plays a critical role in photoreceptor survival and function. RPE deficits are implicated in a wide range of diseases that result in vision loss, including age-related macular degeneration (AMD) and Stargardt disease, affecting millions worldwide. Subretinal delivery of RPE cells is considered a promising avenue for treatment, and encouraging results from animal trials have supported recent progression into the clinic. However, the limited survival and engraftment of transplanted RPE cells delivered as a suspension continues to be a major challenge. While RPE delivery as epithelial sheets exhibits improved outcomes, this comes at the price of increased complexity at both the production and transplant stages. In order to combine the benefits of both approaches, we have developed size-controlled, scaffold-free RPE microtissues (RPE-µTs) that are suitable for scalable production and delivery via injection. RPE-µTs retain key RPE molecular markers, and interestingly, in comparison to conventional monolayer cultures, they show significant increases in the transcription and secretion of pigment-epithelium-derived factor (PEDF), which is a key trophic factor known to enhance the survival and function of photoreceptors. Furthermore, these microtissues readily spread in vitro on a substrate analogous to Bruch’s membrane, suggesting that RPE-µTs may collapse into a sheet upon transplantation. We anticipate that this approach may provide an alternative cell delivery system to improve the survival and integration of RPE transplants, while also retaining the benefits of low complexity in production and delivery.
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spelling pubmed-85836032021-11-12 Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF Al-Ani, Abdullah Toms, Derek Sunba, Saud Giles, Kayla Touahri, Yacine Schuurmans, Carol Ungrin, Mark Int J Mol Sci Article The retinal pigmented epithelium (RPE) plays a critical role in photoreceptor survival and function. RPE deficits are implicated in a wide range of diseases that result in vision loss, including age-related macular degeneration (AMD) and Stargardt disease, affecting millions worldwide. Subretinal delivery of RPE cells is considered a promising avenue for treatment, and encouraging results from animal trials have supported recent progression into the clinic. However, the limited survival and engraftment of transplanted RPE cells delivered as a suspension continues to be a major challenge. While RPE delivery as epithelial sheets exhibits improved outcomes, this comes at the price of increased complexity at both the production and transplant stages. In order to combine the benefits of both approaches, we have developed size-controlled, scaffold-free RPE microtissues (RPE-µTs) that are suitable for scalable production and delivery via injection. RPE-µTs retain key RPE molecular markers, and interestingly, in comparison to conventional monolayer cultures, they show significant increases in the transcription and secretion of pigment-epithelium-derived factor (PEDF), which is a key trophic factor known to enhance the survival and function of photoreceptors. Furthermore, these microtissues readily spread in vitro on a substrate analogous to Bruch’s membrane, suggesting that RPE-µTs may collapse into a sheet upon transplantation. We anticipate that this approach may provide an alternative cell delivery system to improve the survival and integration of RPE transplants, while also retaining the benefits of low complexity in production and delivery. MDPI 2021-10-20 /pmc/articles/PMC8583603/ /pubmed/34768747 http://dx.doi.org/10.3390/ijms222111317 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Al-Ani, Abdullah
Toms, Derek
Sunba, Saud
Giles, Kayla
Touahri, Yacine
Schuurmans, Carol
Ungrin, Mark
Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF
title Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF
title_full Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF
title_fullStr Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF
title_full_unstemmed Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF
title_short Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF
title_sort scaffold-free retinal pigment epithelium microtissues exhibit increased release of pedf
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583603/
https://www.ncbi.nlm.nih.gov/pubmed/34768747
http://dx.doi.org/10.3390/ijms222111317
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