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Transplantation of photoreceptor precursors isolated via a cell surface biomarker panel from embryonic stem cell-derived self-forming retina

Transplantation of photoreceptor precursors isolated via a cell surface biomarker panel from embryonic stem cell-derived self-forming retina
Transplantation of photoreceptor precursors isolated via a cell surface biomarker panel from embryonic stem cell-derived self-forming retina
Loss of photoreceptors due to retinal degeneration is a major cause of untreatable blindness. Cell replacement therapy, using pluripotent stem cell-derived photoreceptor cells, may be a feasible future treatment. Achieving safe and effective cell replacement is critically dependent on the stringent selection and purification of optimal cells for transplantation. Previously, we demonstrated effective transplantation of post-mitotic photoreceptor precursor cells labelled by fluorescent reporter genes. As genetically labelled cells are not desirable for therapy, here we developed a surface biomarker cell selection strategy for application to complex pluripotent stem cell differentiation cultures. We show that a five cell surface biomarker panel CD73(+)CD24(+)CD133(+)CD47(+)CD15(-) facilitates the isolation of photoreceptor precursors from three-dimensional self-forming retina differentiated from mouse embryonic stem cells. Importantly, stem cell-derived cells isolated using the biomarker panel successfully integrate and mature into new rod photoreceptors in the adult mouse retinae after subretinal transplantation. Conversely, unsorted or negatively selected cells do not give rise to newly integrated rods after transplantation. The biomarker panel also removes detrimental proliferating cells prior to transplantation. Notably, we demonstrate how expression of the biomarker panel is conserved in the human retina and propose that a similar selection strategy will facilitate isolation of human transplantation-competent cells for therapeutic application.
1066-5099
2469-2482
Lakowski, Jorn
1856e739-982a-412a-87c7-abf1610f5384
Gonzalez‐Cordero, Anai
3727f8b4-9faf-40af-9846-5e607957de07
West, Emma L.
e9fb2858-50ad-46a1-9aca-5b57d9b32042
Han, Ya‐Ting
5afff4ce-d266-47b1-bc2d-79fa30e8fc6c
Welby, Emily
d687bfd0-f94e-4a55-bc8d-9819bc89f639
Naeem, Arifa
98cddafb-be35-4dbf-aaba-880bee957c58
Blackford, Samuel J.I.
329e8c40-25a8-4170-9c28-8b64364621f8
Bainbridge, James W.B.
be3077b2-2b9c-41de-9f1c-ecb6dda9ad82
Pearson, Rachael A.
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Ali, Robin R.
bddfdcbe-75ce-4264-80cc-c9ef1d6c9d7d
Sowden, Jane C.
e042184a-dbe3-4a58-9f91-c31a5463b893
Lakowski, Jorn
1856e739-982a-412a-87c7-abf1610f5384
Gonzalez‐Cordero, Anai
3727f8b4-9faf-40af-9846-5e607957de07
West, Emma L.
e9fb2858-50ad-46a1-9aca-5b57d9b32042
Han, Ya‐Ting
5afff4ce-d266-47b1-bc2d-79fa30e8fc6c
Welby, Emily
d687bfd0-f94e-4a55-bc8d-9819bc89f639
Naeem, Arifa
98cddafb-be35-4dbf-aaba-880bee957c58
Blackford, Samuel J.I.
329e8c40-25a8-4170-9c28-8b64364621f8
Bainbridge, James W.B.
be3077b2-2b9c-41de-9f1c-ecb6dda9ad82
Pearson, Rachael A.
58e4026c-6312-4b1f-93c5-232e3be982a0
Ali, Robin R.
bddfdcbe-75ce-4264-80cc-c9ef1d6c9d7d
Sowden, Jane C.
e042184a-dbe3-4a58-9f91-c31a5463b893

Lakowski, Jorn, Gonzalez‐Cordero, Anai, West, Emma L., Han, Ya‐Ting, Welby, Emily, Naeem, Arifa, Blackford, Samuel J.I., Bainbridge, James W.B., Pearson, Rachael A., Ali, Robin R. and Sowden, Jane C. (2015) Transplantation of photoreceptor precursors isolated via a cell surface biomarker panel from embryonic stem cell-derived self-forming retina. Stem Cells, 33 (8), 2469-2482. (doi:10.1002/stem.2051).

Record type: Article

Abstract

Loss of photoreceptors due to retinal degeneration is a major cause of untreatable blindness. Cell replacement therapy, using pluripotent stem cell-derived photoreceptor cells, may be a feasible future treatment. Achieving safe and effective cell replacement is critically dependent on the stringent selection and purification of optimal cells for transplantation. Previously, we demonstrated effective transplantation of post-mitotic photoreceptor precursor cells labelled by fluorescent reporter genes. As genetically labelled cells are not desirable for therapy, here we developed a surface biomarker cell selection strategy for application to complex pluripotent stem cell differentiation cultures. We show that a five cell surface biomarker panel CD73(+)CD24(+)CD133(+)CD47(+)CD15(-) facilitates the isolation of photoreceptor precursors from three-dimensional self-forming retina differentiated from mouse embryonic stem cells. Importantly, stem cell-derived cells isolated using the biomarker panel successfully integrate and mature into new rod photoreceptors in the adult mouse retinae after subretinal transplantation. Conversely, unsorted or negatively selected cells do not give rise to newly integrated rods after transplantation. The biomarker panel also removes detrimental proliferating cells prior to transplantation. Notably, we demonstrate how expression of the biomarker panel is conserved in the human retina and propose that a similar selection strategy will facilitate isolation of human transplantation-competent cells for therapeutic application.

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Lakowski et al 2015 STEM CELLS - Version of Record
Available under License Creative Commons Attribution.
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e-pub ahead of print date: 18 May 2015
Published date: August 2015

Identifiers

Local EPrints ID: 425771
URI: http://eprints.soton.ac.uk/id/eprint/425771
ISSN: 1066-5099
PURE UUID: 5bc9655a-f511-43fb-b8b1-85b88e8dd7c5
ORCID for Jorn Lakowski: ORCID iD orcid.org/0000-0003-4214-7580

Catalogue record

Date deposited: 02 Nov 2018 17:30
Last modified: 22 Nov 2021 03:18

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Contributors

Author: Jorn Lakowski ORCID iD
Author: Anai Gonzalez‐Cordero
Author: Emma L. West
Author: Ya‐Ting Han
Author: Emily Welby
Author: Arifa Naeem
Author: Samuel J.I. Blackford
Author: James W.B. Bainbridge
Author: Rachael A. Pearson
Author: Robin R. Ali
Author: Jane C. Sowden

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