Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration.

Details

Serval ID
serval:BIB_16E08B9BA2B7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Differentiation and Transplantation of Embryonic Stem Cell-Derived Cone Photoreceptors into a Mouse Model of End-Stage Retinal Degeneration.
Journal
Stem cell reports
Author(s)
Kruczek K., Gonzalez-Cordero A., Goh D., Naeem A., Jonikas M., Blackford SJI, Kloc M., Duran Y., Georgiadis A., Sampson R.D., Maswood R.N., Smith A.J., Decembrini S., Arsenijevic Y., Sowden J.C., Pearson R.A., West E.L., Ali R.R.
ISSN
2213-6711 (Electronic)
ISSN-L
2213-6711
Publication state
Published
Issued date
06/06/2017
Peer-reviewed
Oui
Volume
8
Number
6
Pages
1659-1674
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The loss of cone photoreceptors that mediate daylight vision represents a leading cause of blindness, for which cell replacement by transplantation offers a promising treatment strategy. Here, we characterize cone differentiation in retinas derived from mouse embryonic stem cells (mESCs). Similar to in vivo development, a temporal pattern of progenitor marker expression is followed by the differentiation of early thyroid hormone receptor β2-positive precursors and, subsequently, photoreceptors exhibiting cone-specific phototransduction-related proteins. We establish that stage-specific inhibition of the Notch pathway increases cone cell differentiation, while retinoic acid signaling regulates cone maturation, comparable with their actions in vivo. MESC-derived cones can be isolated in large numbers and transplanted into adult mouse eyes, showing capacity to survive and mature in the subretinal space of Aipl1-/- mice, a model of end-stage retinal degeneration. Together, this work identifies a robust, renewable cell source for cone replacement by purified cell suspension transplantation.

Keywords
Adaptor Proteins, Signal Transducing/deficiency, Adaptor Proteins, Signal Transducing/genetics, Animals, Basic-Leucine Zipper Transcription Factors/antagonists & inhibitors, Basic-Leucine Zipper Transcription Factors/genetics, Basic-Leucine Zipper Transcription Factors/metabolism, Cell Differentiation/drug effects, Disease Models, Animal, Eye Proteins/antagonists & inhibitors, Eye Proteins/genetics, Eye Proteins/metabolism, Hepatocyte Nuclear Factor 6/metabolism, Leukemia Inhibitory Factor/pharmacology, Mice, Mice, Knockout, Mouse Embryonic Stem Cells/cytology, Mouse Embryonic Stem Cells/transplantation, Oligodendrocyte Transcription Factor 2/metabolism, Opsins/metabolism, Orphan Nuclear Receptors/antagonists & inhibitors, Orphan Nuclear Receptors/genetics, Orphan Nuclear Receptors/metabolism, Otx Transcription Factors/metabolism, RNA Interference, RNA, Small Interfering/metabolism, Receptors, Notch/antagonists & inhibitors, Receptors, Notch/metabolism, Retinal Cone Photoreceptor Cells/cytology, Retinal Cone Photoreceptor Cells/metabolism, Retinal Degeneration/pathology, Retinal Degeneration/therapy, Signal Transduction, Tretinoin/metabolism, Tretinoin/pharmacology, blindness, cell- and tissue-based therapy, mouse embryonic stem cells, retina, retinal cone photoreceptor cells, retinal degeneration
Pubmed
Web of science
Open Access
Yes
Create date
26/06/2017 17:42
Last modification date
20/08/2019 13:46
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