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Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients

Klassen, Henry; Kiilgaard, Jens Folke; Zahir, Tasneem; Ziaeian, Boback; Kirov, Ivan; Scherfig, Erik; Warfvinge, Karin LU and Young, Michael J. (2007) In Stem Cells 25(5). p.1222-1230
Abstract
Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor cells from the neural retina of the domestic pig and transplanted them to the laser-injured retina of allorecipients. Prior to grafting, immunocytochemical analysis showed that cultured porcine RPCs widely expressed neural cell adhesion molecule, as well as markers consistent with immature neural cells, including nestin, Sox2, and vimentin. Subpopulations expressed the neurodevelopmental markers CD-15, doublecortin, beta-III tubulin, and glial... (More)
Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor cells from the neural retina of the domestic pig and transplanted them to the laser-injured retina of allorecipients. Prior to grafting, immunocytochemical analysis showed that cultured porcine RPCs widely expressed neural cell adhesion molecule, as well as markers consistent with immature neural cells, including nestin, Sox2, and vimentin. Subpopulations expressed the neurodevelopmental markers CD-15, doublecortin, beta-III tubulin, and glial fibrillary acidic protein. Retina-specific markers expressed included the bipolar marker protein kinase C alpha and the photoreceptor-associated markers recoverin and rhodopsin. In addition, reverse transcription-polymerase chain reaction showed expression of the transcription factors Dach1, Hes1, Lhx2, Pax6, Six3, and Six6. Progenitor cells prelabeled with vital dyes survived as allografts in the subretinal space for up to 5 weeks (11 of 12 recipients) without exogenous immune suppression. Grafted cells expressed transducin, recoverin, and rhodopsin in the pig subretinal space, suggestive of differentiation into photoreceptors or, in a few cases, migrated into the neural retina and extended processes, the latter typically showing radial orientation. These results demonstrate that many of the findings seen with rodent RPCs can be duplicated in a large mammal. The pig offers a number of advantages over mice and rats, particularly in terms of functional testing and evaluation of the potential for clinical translation to human subjects. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
transducin, recoverin, rhodopsin, stem cells, photoreceptor, swine
in
Stem Cells
volume
25
issue
5
pages
1222 - 1230
publisher
AlphaMed Press
external identifiers
  • wos:000246292700016
  • scopus:34247577499
ISSN
1549-4918
DOI
10.1634/stemcells.2006-0541
language
English
LU publication?
yes
id
61314c9f-201a-4424-90d0-8ae2c2d2f165 (old id 661058)
date added to LUP
2007-12-13 17:02:28
date last changed
2017-11-12 03:59:11
@article{61314c9f-201a-4424-90d0-8ae2c2d2f165,
  abstract     = {Work in rodents has shown that cultured retinal progenitor cells (RPCs) integrate into the degenerating retina, thus suggesting a potential strategy for treatment of similar degenerative conditions in humans. To demonstrate the relevance of the rodent work to large animals, we derived progenitor cells from the neural retina of the domestic pig and transplanted them to the laser-injured retina of allorecipients. Prior to grafting, immunocytochemical analysis showed that cultured porcine RPCs widely expressed neural cell adhesion molecule, as well as markers consistent with immature neural cells, including nestin, Sox2, and vimentin. Subpopulations expressed the neurodevelopmental markers CD-15, doublecortin, beta-III tubulin, and glial fibrillary acidic protein. Retina-specific markers expressed included the bipolar marker protein kinase C alpha and the photoreceptor-associated markers recoverin and rhodopsin. In addition, reverse transcription-polymerase chain reaction showed expression of the transcription factors Dach1, Hes1, Lhx2, Pax6, Six3, and Six6. Progenitor cells prelabeled with vital dyes survived as allografts in the subretinal space for up to 5 weeks (11 of 12 recipients) without exogenous immune suppression. Grafted cells expressed transducin, recoverin, and rhodopsin in the pig subretinal space, suggestive of differentiation into photoreceptors or, in a few cases, migrated into the neural retina and extended processes, the latter typically showing radial orientation. These results demonstrate that many of the findings seen with rodent RPCs can be duplicated in a large mammal. The pig offers a number of advantages over mice and rats, particularly in terms of functional testing and evaluation of the potential for clinical translation to human subjects.},
  author       = {Klassen, Henry and Kiilgaard, Jens Folke and Zahir, Tasneem and Ziaeian, Boback and Kirov, Ivan and Scherfig, Erik and Warfvinge, Karin and Young, Michael J.},
  issn         = {1549-4918},
  keyword      = {transducin,recoverin,rhodopsin,stem cells,photoreceptor,swine},
  language     = {eng},
  number       = {5},
  pages        = {1222--1230},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {Progenitor cells from the porcine neural retina express photoreceptor markers after transplantation to the subretinal space of allorecipients},
  url          = {http://dx.doi.org/10.1634/stemcells.2006-0541},
  volume       = {25},
  year         = {2007},
}