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

¹ Stem Cell Research, Children's Hospital of Orange Country, Orange, California; Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
² Eye Department, Rigshospitalet and Eye Pathology Inst, Copenhagen University, Copenhagen, Denmark
³ Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
⁴ Stem Cell Research, Children's Hospital of Orange Country, Orange, California
⁵ Wallenberg Retina Center, Department of Ophthalmology, Lund University, Lund, Sweden

^* To whom correspondence should be addressed. E-mail: hklassen{at}uci.edu.

	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. In order 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 NCAM as well as markers consistent with immature neural cells including nestin, Sox2, and vimentin. Subpopulations expressed the neurodevelopmental markers CD-15, doublecortin, -III tubulin, as well as GFAP. Retina-specific markers expressed included the bipolar marker PKC and the photoreceptor-associated markers recoverin and rhodopsin. In addition, RT-PCR showed expression of the transcription factors Dach1, Hes1, Lhx2, Pax6, Six3, and Six6. Progenitor cells pre-labeled with vital dyes survived as allografts in the subretinal space for up to 5 weeks (11/12 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.

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