The University of Southampton
University of Southampton Institutional Repository

Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina

Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina
Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina

Irreversible blindness caused by loss of photoreceptors may be amenable to cell therapy. We previously demonstrated retinal repair and restoration of vision through transplantation of photoreceptor precursors obtained from postnatal retinas into visually impaired adult mice. Considerable progress has been made in differentiating embryonic stem cells (ESCs) in vitro toward photoreceptor lineages. However, the capability of ESC-derived photoreceptors to integrate after transplantation has not been demonstrated unequivocally. Here, to isolate photoreceptor precursors fit for transplantation, we adapted a recently reported three-dimensional (3D) differentiation protocol that generates neuroretina from mouse ESCs. We show that rod precursors derived by this protocol and selected via a GFP reporter under the control of a Rhodopsin promoter integrate within degenerate retinas of adult mice and mature into outer segment-bearing photoreceptors. Notably, ESC-derived precursors at a developmental stage similar to postnatal days 4-8 integrate more efficiently compared with cells at other stages. This study shows conclusively that ESCs can provide a source of photoreceptors for retinal cell transplantation.

Animals, Blindness/genetics, Cell Culture Techniques, Cell Differentiation, Cell- and Tissue-Based Therapy, Embryonic Stem Cells/cytology, Green Fluorescent Proteins, Mice, Photoreceptor Cells, Photoreceptor Cells, Vertebrate, Retina/cytology, Rhodopsin/genetics, Stem Cell Transplantation
1087-0156
741-747
Gonzalez-Cordero, Anai
3727f8b4-9faf-40af-9846-5e607957de07
West, Emma L.
e9fb2858-50ad-46a1-9aca-5b57d9b32042
Pearson, Rachael A.
4b8c2476-e361-42e4-a4cb-71208646d06a
Duran, Yanai
16d2c404-658b-44e7-9bf0-ddf55952777a
Carvalho, Livia S.
addfc61a-9616-4a90-9557-a42addf40e95
Chu, Colin J.
d69c53b5-b2dc-40fb-92cf-629a287bcae9
Naeem, Arifa
98cddafb-be35-4dbf-aaba-880bee957c58
Blackford, Samuel J.I.
329e8c40-25a8-4170-9c28-8b64364621f8
Georgiadis, Anastasios
c233db3f-abcb-473e-b5cc-7891a59379eb
Lakowski, Jorn
1856e739-982a-412a-87c7-abf1610f5384
Hubank, Mike
ce4812f2-faca-42d9-ac80-7b5109698992
Smith, Alexander J.
c563d9b8-d59d-4367-9fb4-328d350dd7d8
Bainbridge, James W.B.
be3077b2-2b9c-41de-9f1c-ecb6dda9ad82
Sowden, Jane C.
e042184a-dbe3-4a58-9f91-c31a5463b893
Ali, Robin R.
bddfdcbe-75ce-4264-80cc-c9ef1d6c9d7d
Gonzalez-Cordero, Anai
3727f8b4-9faf-40af-9846-5e607957de07
West, Emma L.
e9fb2858-50ad-46a1-9aca-5b57d9b32042
Pearson, Rachael A.
4b8c2476-e361-42e4-a4cb-71208646d06a
Duran, Yanai
16d2c404-658b-44e7-9bf0-ddf55952777a
Carvalho, Livia S.
addfc61a-9616-4a90-9557-a42addf40e95
Chu, Colin J.
d69c53b5-b2dc-40fb-92cf-629a287bcae9
Naeem, Arifa
98cddafb-be35-4dbf-aaba-880bee957c58
Blackford, Samuel J.I.
329e8c40-25a8-4170-9c28-8b64364621f8
Georgiadis, Anastasios
c233db3f-abcb-473e-b5cc-7891a59379eb
Lakowski, Jorn
1856e739-982a-412a-87c7-abf1610f5384
Hubank, Mike
ce4812f2-faca-42d9-ac80-7b5109698992
Smith, Alexander J.
c563d9b8-d59d-4367-9fb4-328d350dd7d8
Bainbridge, James W.B.
be3077b2-2b9c-41de-9f1c-ecb6dda9ad82
Sowden, Jane C.
e042184a-dbe3-4a58-9f91-c31a5463b893
Ali, Robin R.
bddfdcbe-75ce-4264-80cc-c9ef1d6c9d7d

Gonzalez-Cordero, Anai, West, Emma L., Pearson, Rachael A., Duran, Yanai, Carvalho, Livia S., Chu, Colin J., Naeem, Arifa, Blackford, Samuel J.I., Georgiadis, Anastasios, Lakowski, Jorn, Hubank, Mike, Smith, Alexander J., Bainbridge, James W.B., Sowden, Jane C. and Ali, Robin R. (2014) Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nature Biotechnology, 31 (8), 741-747. (doi:10.1038/nbt.2643).

Record type: Article

Abstract

Irreversible blindness caused by loss of photoreceptors may be amenable to cell therapy. We previously demonstrated retinal repair and restoration of vision through transplantation of photoreceptor precursors obtained from postnatal retinas into visually impaired adult mice. Considerable progress has been made in differentiating embryonic stem cells (ESCs) in vitro toward photoreceptor lineages. However, the capability of ESC-derived photoreceptors to integrate after transplantation has not been demonstrated unequivocally. Here, to isolate photoreceptor precursors fit for transplantation, we adapted a recently reported three-dimensional (3D) differentiation protocol that generates neuroretina from mouse ESCs. We show that rod precursors derived by this protocol and selected via a GFP reporter under the control of a Rhodopsin promoter integrate within degenerate retinas of adult mice and mature into outer segment-bearing photoreceptors. Notably, ESC-derived precursors at a developmental stage similar to postnatal days 4-8 integrate more efficiently compared with cells at other stages. This study shows conclusively that ESCs can provide a source of photoreceptors for retinal cell transplantation.

This record has no associated files available for download.

More information

e-pub ahead of print date: 25 July 2013
Published date: 2014
Keywords: Animals, Blindness/genetics, Cell Culture Techniques, Cell Differentiation, Cell- and Tissue-Based Therapy, Embryonic Stem Cells/cytology, Green Fluorescent Proteins, Mice, Photoreceptor Cells, Photoreceptor Cells, Vertebrate, Retina/cytology, Rhodopsin/genetics, Stem Cell Transplantation

Identifiers

Local EPrints ID: 431029
URI: http://eprints.soton.ac.uk/id/eprint/431029
ISSN: 1087-0156
PURE UUID: dca0540a-2cb6-4954-8935-44074c03b0a6
ORCID for Jorn Lakowski: ORCID iD orcid.org/0000-0003-4214-7580

Catalogue record

Date deposited: 22 May 2019 16:30
Last modified: 28 Apr 2022 02:21

Export record

Altmetrics

Contributors

Author: Anai Gonzalez-Cordero
Author: Emma L. West
Author: Rachael A. Pearson
Author: Yanai Duran
Author: Livia S. Carvalho
Author: Colin J. Chu
Author: Arifa Naeem
Author: Samuel J.I. Blackford
Author: Anastasios Georgiadis
Author: Jorn Lakowski ORCID iD
Author: Mike Hubank
Author: Alexander J. Smith
Author: James W.B. Bainbridge
Author: Jane C. Sowden
Author: Robin R. Ali

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×