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:	Abdullah Al-Ani, Derek Toms, Saud Sunba, Kayla Giles, Yacine Touahri, Carol Schuurmans, Mark Ungrin
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	RPE microtissue retina tissue engineering ESC-RPE ARPE-19 Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/16d0ad101db2490ba6e8dec276be27c6
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spelling	oai:doaj.org-article:16d0ad101db2490ba6e8dec276be27c62021-11-11T16:48:20ZScaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF10.3390/ijms2221113171422-00671661-6596https://doaj.org/article/16d0ad101db2490ba6e8dec276be27c62021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11317https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067The 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.Abdullah Al-AniDerek TomsSaud SunbaKayla GilesYacine TouahriCarol SchuurmansMark UngrinMDPI AGarticleRPEmicrotissueretinatissue engineeringESC-RPEARPE-19Biology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11317, p 11317 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	RPE microtissue retina tissue engineering ESC-RPE ARPE-19 Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	RPE microtissue retina tissue engineering ESC-RPE ARPE-19 Biology (General) QH301-705.5 Chemistry QD1-999 Abdullah Al-Ani Derek Toms Saud Sunba Kayla Giles Yacine Touahri Carol Schuurmans Mark Ungrin Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF
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.
format	article
author	Abdullah Al-Ani Derek Toms Saud Sunba Kayla Giles Yacine Touahri Carol Schuurmans Mark Ungrin
author_facet	Abdullah Al-Ani Derek Toms Saud Sunba Kayla Giles Yacine Touahri Carol Schuurmans Mark Ungrin
author_sort	Abdullah Al-Ani
title	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_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_sort	scaffold-free retinal pigment epithelium microtissues exhibit increased release of pedf
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/16d0ad101db2490ba6e8dec276be27c6
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Scaffold-Free Retinal Pigment Epithelium Microtissues Exhibit Increased Release of PEDF

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