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Adult limbal neurosphere cells: a potential autologous cell resource for retinal cell generation

Adult limbal neurosphere cells: a potential autologous cell resource for retinal cell generation
Adult limbal neurosphere cells: a potential autologous cell resource for retinal cell generation
The Corneal limbus is a readily accessible region at the front of the eye, separating the cornea and sclera. Neural colonies (neurospheres) can be generated from adult corneal limbus in vitro. We have previously shown that these neurospheres originate from neural crest stem/progenitor cells and that they can differentiate into functional neurons in vitro. The aim of this study was to investigate whether mouse and human limbal neurosphere cells (LNS) could differentiate towards a retinal lineage both in vivo and in vitro following exposure to a developing retinal microenvironment. In this article we show that LNS can be generated from adult mice and aged humans (up to 97 years) using a serum free culture assay. Following culture with developing mouse retinal cells, we detected retinal progenitor cell markers, mature retinal/neuronal markers and sensory cilia in the majority of mouse LNS experiments. After transplantation into the sub-retinal space of neonatal mice, mouse LNS cells expressed photoreceptor specific markers, but no incorporation into host retinal tissue was seen. Human LNS cells also expressed retinal progenitor markers at the transcription level but mature retinal markers were not observed in vitro or in vivo. This data highlights that mouse corneal limbal stromal progenitor cells can transdifferentiate towards a retinal lineage. Complete differentiation is likely to require more comprehensive regulation; however, the accessibility and plasticity of LNS makes them an attractive cell resource for future study and ultimately therapeutic application.
1932-6203
e1084
Chen, Xiaoli
fba6c7fa-57f3-4f56-838e-fbb787004fec
Thomson, Heather
8914c4e4-b602-4ecc-a99d-897ed0fdd472
Cooke, J.J.
944d492e-88f3-41f2-a00d-e22407ca7605
Scott, Jennifer A.
a8d2adb9-5eb1-4efd-bc65-5dde57b12fc1
Hossain, Parwez
563de5fc-84ad-4539-9228-bde0237eaf51
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514
Chen, Xiaoli
fba6c7fa-57f3-4f56-838e-fbb787004fec
Thomson, Heather
8914c4e4-b602-4ecc-a99d-897ed0fdd472
Cooke, J.J.
944d492e-88f3-41f2-a00d-e22407ca7605
Scott, Jennifer A.
a8d2adb9-5eb1-4efd-bc65-5dde57b12fc1
Hossain, Parwez
563de5fc-84ad-4539-9228-bde0237eaf51
Lotery, Andrew J.
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514

Chen, Xiaoli, Thomson, Heather, Cooke, J.J., Scott, Jennifer A., Hossain, Parwez and Lotery, Andrew J. (2014) Adult limbal neurosphere cells: a potential autologous cell resource for retinal cell generation. PLoS ONE, 9 (10), e1084. (doi:10.1371/journal.pone.0108418). (PMID:25271851)

Record type: Article

Abstract

The Corneal limbus is a readily accessible region at the front of the eye, separating the cornea and sclera. Neural colonies (neurospheres) can be generated from adult corneal limbus in vitro. We have previously shown that these neurospheres originate from neural crest stem/progenitor cells and that they can differentiate into functional neurons in vitro. The aim of this study was to investigate whether mouse and human limbal neurosphere cells (LNS) could differentiate towards a retinal lineage both in vivo and in vitro following exposure to a developing retinal microenvironment. In this article we show that LNS can be generated from adult mice and aged humans (up to 97 years) using a serum free culture assay. Following culture with developing mouse retinal cells, we detected retinal progenitor cell markers, mature retinal/neuronal markers and sensory cilia in the majority of mouse LNS experiments. After transplantation into the sub-retinal space of neonatal mice, mouse LNS cells expressed photoreceptor specific markers, but no incorporation into host retinal tissue was seen. Human LNS cells also expressed retinal progenitor markers at the transcription level but mature retinal markers were not observed in vitro or in vivo. This data highlights that mouse corneal limbal stromal progenitor cells can transdifferentiate towards a retinal lineage. Complete differentiation is likely to require more comprehensive regulation; however, the accessibility and plasticity of LNS makes them an attractive cell resource for future study and ultimately therapeutic application.

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e-pub ahead of print date: 1 October 2014
Published date: 1 October 2014
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 369962
URI: https://eprints.soton.ac.uk/id/eprint/369962
ISSN: 1932-6203
PURE UUID: b5258d1f-ad26-4bdd-8901-12e15c5860b2
ORCID for Parwez Hossain: ORCID iD orcid.org/0000-0002-3131-2395
ORCID for Andrew J. Lotery: ORCID iD orcid.org/0000-0001-5541-4305

Catalogue record

Date deposited: 15 Oct 2014 10:17
Last modified: 07 Aug 2019 00:43

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