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Effective Transplantation of Photoreceptor Precursor Cells Selected via Cell Surface Antigen Expression

Effective Transplantation of Photoreceptor Precursor Cells Selected via Cell Surface Antigen Expression
Effective Transplantation of Photoreceptor Precursor Cells Selected via Cell Surface Antigen Expression
Retinal degenerative diseases are a major cause of untreatable blindness. Stem cell therapy to replace lost photoreceptors represents a feasible future treatment. We previously demonstrated that postmitotic photoreceptor precursors expressing an NrlGFP transgene integrate into the diseased retina and restore some light sensitivity. As genetic modification of precursor cells derived from stem cell cultures is not desirable for therapy, we have tested cell selection strategies using fluorochrome‐conjugated antibodies recognizing cell surface antigens to sort photoreceptor precursors. Microarray analysis of postnatal NrlGFP‐expressing precursors identified four candidate genes encoding cell surface antigens (Nt5e, Prom1, Podxl, and Cd24a). To test the feasibility of using donor cells isolated using cell surface markers for retinal therapy, cells selected from developing retinae by fluorescence‐activated cell sorting based on Cd24a expression (using CD24 antibody) and/or Nt5e expression (using CD73 antibody) were transplanted into the wild‐type or Crb1rd8/rd8 or Prph2rd2/rd2 mouse eye. The CD73/CD24‐sorted cells migrated into the outer nuclear layer, acquired the morphology of mature photoreceptors and expressed outer segment markers. They showed an 18‐fold higher integration efficiency than that of unsorted cells and 2.3‐fold higher than cells sorted based on a single genetic marker, NrlGFP, expression. These proof‐of‐principle studies show that transplantation competent photoreceptor precursor cells can be efficiently isolated from a heterogeneous mix of cells using cell surface antigens without loss of viability for the purpose of retinal stem cell therapy. Refinement of the selection of donorphotoreceptor precursor cells can increase the number of integrated photoreceptor cells,which is a prerequisite for the restoration of sight.
1066-5099
1391-1404
Lakowski, Jorn
1856e739-982a-412a-87c7-abf1610f5384
Lakowski, Jorn
1856e739-982a-412a-87c7-abf1610f5384

Lakowski, Jorn (2011) Effective Transplantation of Photoreceptor Precursor Cells Selected via Cell Surface Antigen Expression. Stem Cells, 29 (9), 1391-1404. (doi:10.1002/stem.694).

Record type: Article

Abstract

Retinal degenerative diseases are a major cause of untreatable blindness. Stem cell therapy to replace lost photoreceptors represents a feasible future treatment. We previously demonstrated that postmitotic photoreceptor precursors expressing an NrlGFP transgene integrate into the diseased retina and restore some light sensitivity. As genetic modification of precursor cells derived from stem cell cultures is not desirable for therapy, we have tested cell selection strategies using fluorochrome‐conjugated antibodies recognizing cell surface antigens to sort photoreceptor precursors. Microarray analysis of postnatal NrlGFP‐expressing precursors identified four candidate genes encoding cell surface antigens (Nt5e, Prom1, Podxl, and Cd24a). To test the feasibility of using donor cells isolated using cell surface markers for retinal therapy, cells selected from developing retinae by fluorescence‐activated cell sorting based on Cd24a expression (using CD24 antibody) and/or Nt5e expression (using CD73 antibody) were transplanted into the wild‐type or Crb1rd8/rd8 or Prph2rd2/rd2 mouse eye. The CD73/CD24‐sorted cells migrated into the outer nuclear layer, acquired the morphology of mature photoreceptors and expressed outer segment markers. They showed an 18‐fold higher integration efficiency than that of unsorted cells and 2.3‐fold higher than cells sorted based on a single genetic marker, NrlGFP, expression. These proof‐of‐principle studies show that transplantation competent photoreceptor precursor cells can be efficiently isolated from a heterogeneous mix of cells using cell surface antigens without loss of viability for the purpose of retinal stem cell therapy. Refinement of the selection of donorphotoreceptor precursor cells can increase the number of integrated photoreceptor cells,which is a prerequisite for the restoration of sight.

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More information

e-pub ahead of print date: 19 July 2011
Published date: September 2011

Identifiers

Local EPrints ID: 425770
URI: http://eprints.soton.ac.uk/id/eprint/425770
ISSN: 1066-5099
PURE UUID: 930ec9ff-29f5-488c-8c8e-d6d531896a43
ORCID for Jorn Lakowski: ORCID iD orcid.org/0000-0003-4214-7580

Catalogue record

Date deposited: 02 Nov 2018 17:30
Last modified: 10 Nov 2021 03:50

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