Retinal stem cells transplanted into models of late stages of retinitis pigmentosa preferentially adopt a glial or a retinal ganglion cell fate

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Serval ID
serval:BIB_C54F514C6124
Type
Article: article from journal or magazin.
Collection
Publications
Title
Retinal stem cells transplanted into models of late stages of retinitis pigmentosa preferentially adopt a glial or a retinal ganglion cell fate
Journal
Investigative Ophthalmology and Visual Science
Author(s)
Canola K., Angenieux B., Tekaya M., Quiambao A., Naash M. I., Munier F. L., Schorderet D. F., Arsenijevic Y.
ISSN
0146-0404 (Print)
Publication state
Published
Issued date
01/2007
Peer-reviewed
Oui
Volume
48
Number
1
Pages
446-54
Language
english
Notes
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Jan
Abstract
PURPOSE: To characterize the potential of newborn retinal stem cells (RSCs) isolated from the radial glia population to integrate the retina, this study was conducted to investigate the fate of in vitro expanded RSCs transplanted into retinas devoid of photoreceptors (adult rd1 and old VPP mice and rhodopsin-mutated transgenic mice) or partially degenerated retina (adult VPP mice) retinas. METHODS: Populations of RSCs and progenitor cells were isolated either from DBA2J newborn mice and labeled with the red lipophilic fluorescent dye (PKH26) or from GFP (green fluorescent protein) transgenic mice. After expansion in EGF+FGF2 (epidermal growth factor+fibroblast growth factor), cells were transplanted intravitreally or subretinally into the eyes of adult wild-type, transgenic mice undergoing slow (VPP strain) or rapid (rd1 strain) retinal degeneration. RESULTS: Only limited migration and differentiation of the cells were observed in normal mice injected subretinally or in VPP and rd1 mice injected intravitreally. After subretinal injection in old VPP mice, transplanted cells massively migrated into the ganglion cell layer and, at 1 and 4 weeks after injection, harbored neuronal and glial markers expressed locally, such as beta-tubulin-III, NeuN, Brn3b, or glial fibrillary acidic protein (GFAP), with a marked preference for the glial phenotype. In adult VPP retinas, the grafted cells behaved similarly. Few grafted cells stayed in the degenerating outer nuclear layer (ONL). These cells were, in rare cases, positive for rhodopsin or recoverin, markers specific for photoreceptors and some bipolar cells. CONCLUSIONS: These results show that the grafted cells preferentially integrate into the GCL and IPL and express ganglion cell or glial markers, thus exhibiting migratory and differentiation preferences when injected subretinally. It also appears that the retina, whether partially degenerated or already degenerated, does not provide signals to induce massive differentiation of RSCs into photoreceptors. This observation suggests that a predifferentiation of RSCs into photoreceptors before transplantation may be necessary to obtain graft integration in the ONL.
Keywords
Animals Animals, Newborn Biological Markers/metabolism Cell Differentiation/physiology Cell Movement/physiology Cell Survival *Disease Models, Animal Fluorescent Dyes Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Mutant Strains Mice, Transgenic Microscopy, Fluorescence Nerve Tissue Proteins/metabolism Neuroglia/*cytology/metabolism Phenotype Retina/*cytology Retinal Ganglion Cells/*cytology/metabolism Retinitis Pigmentosa/metabolism/pathology/*surgery *Stem Cell Transplantation Stem Cells/*physiology
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 12:59
Last modification date
20/08/2019 15:40
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