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Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival

We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factor...

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Autores principales: Ma, Jie, Guo, Chenying, Guo, Caiwei, Sun, Yu, Liao, Tiffany, Beattie, Ursula, López, Francisco J., Chen, Dong Feng, Lashkari, Kameran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414591/
https://www.ncbi.nlm.nih.gov/pubmed/25923430
http://dx.doi.org/10.1371/journal.pone.0125695
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author Ma, Jie
Guo, Chenying
Guo, Caiwei
Sun, Yu
Liao, Tiffany
Beattie, Ursula
López, Francisco J.
Chen, Dong Feng
Lashkari, Kameran
author_facet Ma, Jie
Guo, Chenying
Guo, Caiwei
Sun, Yu
Liao, Tiffany
Beattie, Ursula
López, Francisco J.
Chen, Dong Feng
Lashkari, Kameran
author_sort Ma, Jie
collection PubMed
description We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNP(IGF-TD) cells displayed enhanced survival, and increased neurite extension and branching as compared to hNP(TD) or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNP(IGF-TD) cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNP(IGF-TD) cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma.
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spelling pubmed-44145912015-05-07 Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival Ma, Jie Guo, Chenying Guo, Caiwei Sun, Yu Liao, Tiffany Beattie, Ursula López, Francisco J. Chen, Dong Feng Lashkari, Kameran PLoS One Research Article We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNP(IGF-TD) cells displayed enhanced survival, and increased neurite extension and branching as compared to hNP(TD) or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNP(IGF-TD) cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNP(IGF-TD) cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma. Public Library of Science 2015-04-29 /pmc/articles/PMC4414591/ /pubmed/25923430 http://dx.doi.org/10.1371/journal.pone.0125695 Text en © 2015 Ma et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ma, Jie
Guo, Chenying
Guo, Caiwei
Sun, Yu
Liao, Tiffany
Beattie, Ursula
López, Francisco J.
Chen, Dong Feng
Lashkari, Kameran
Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival
title Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival
title_full Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival
title_fullStr Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival
title_full_unstemmed Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival
title_short Transplantation of Human Neural Progenitor Cells Expressing IGF-1 Enhances Retinal Ganglion Cell Survival
title_sort transplantation of human neural progenitor cells expressing igf-1 enhances retinal ganglion cell survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414591/
https://www.ncbi.nlm.nih.gov/pubmed/25923430
http://dx.doi.org/10.1371/journal.pone.0125695
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