Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct

Work has shown that stem cell transplantation can rescue or replace neurons in models of retinal degenerative disease. Neural progenitor cells (NPCs) modified to overexpress neurotrophic factors are one means of providing sustained delivery of therapeutic gene products in vivo. To develop a nonroden...

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Main Authors: X. Joann You, Ping Gu, Jinmei Wang, Tianran Song, Jing Yang, Chee Gee Liew, Henry Klassen
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Journal of Ophthalmology
Online Access:http://dx.doi.org/10.1155/2011/378965
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author X. Joann You
Ping Gu
Jinmei Wang
Tianran Song
Jing Yang
Chee Gee Liew
Henry Klassen
author_facet X. Joann You
Ping Gu
Jinmei Wang
Tianran Song
Jing Yang
Chee Gee Liew
Henry Klassen
author_sort X. Joann You
collection DOAJ
description Work has shown that stem cell transplantation can rescue or replace neurons in models of retinal degenerative disease. Neural progenitor cells (NPCs) modified to overexpress neurotrophic factors are one means of providing sustained delivery of therapeutic gene products in vivo. To develop a nonrodent animal model of this therapeutic strategy, we previously derived NPCs from the fetal cat brain (cNPCs). Here we use bicistronic feline lentiviral vectors to transduce cNPCs with glial cell-derived neurotrophic factor (GDNF) together with a GFP reporter gene. Transduction efficacy is assessed, together with transgene expression level and stability during induction of cellular differentiation, together with the influence of GDNF transduction on growth and gene expression profile. We show that GDNF overexpressing cNPCs expand in vitro, coexpress GFP, and secrete high levels of GDNF protein—before and after differentiation—all qualities advantageous for use as a cell-based approach in feline models of neural degenerative disease.
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spelling doaj-art-00a3ec5c51744879a777a1a781f9eaee2025-08-20T03:22:31ZengWileyJournal of Ophthalmology2090-004X2090-00582011-01-01201110.1155/2011/378965378965Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral ConstructX. Joann You0Ping Gu1Jinmei Wang2Tianran Song3Jing Yang4Chee Gee Liew5Henry Klassen6Department of Ophthalmology, School of Medicine, Gavin Herbert Eye Institute, University of California, Irvine, 101 The City Drive, Bldg. 55, 2nd Fl, Orange, CA 92868-4380, USADepartment of Ophthalmology, School of Medicine, Gavin Herbert Eye Institute, University of California, Irvine, 101 The City Drive, Bldg. 55, 2nd Fl, Orange, CA 92868-4380, USADepartment of Ophthalmology, School of Medicine, Gavin Herbert Eye Institute, University of California, Irvine, 101 The City Drive, Bldg. 55, 2nd Fl, Orange, CA 92868-4380, USADepartment of Ophthalmology, School of Medicine, Gavin Herbert Eye Institute, University of California, Irvine, 101 The City Drive, Bldg. 55, 2nd Fl, Orange, CA 92868-4380, USADepartment of Ophthalmology, School of Medicine, Gavin Herbert Eye Institute, University of California, Irvine, 101 The City Drive, Bldg. 55, 2nd Fl, Orange, CA 92868-4380, USADepartment of Cell Biology and Neuroscience, Stem Cell Center, University of California, Riverside, Riverside, CA 92521, USADepartment of Ophthalmology, School of Medicine, Gavin Herbert Eye Institute, University of California, Irvine, 101 The City Drive, Bldg. 55, 2nd Fl, Orange, CA 92868-4380, USAWork has shown that stem cell transplantation can rescue or replace neurons in models of retinal degenerative disease. Neural progenitor cells (NPCs) modified to overexpress neurotrophic factors are one means of providing sustained delivery of therapeutic gene products in vivo. To develop a nonrodent animal model of this therapeutic strategy, we previously derived NPCs from the fetal cat brain (cNPCs). Here we use bicistronic feline lentiviral vectors to transduce cNPCs with glial cell-derived neurotrophic factor (GDNF) together with a GFP reporter gene. Transduction efficacy is assessed, together with transgene expression level and stability during induction of cellular differentiation, together with the influence of GDNF transduction on growth and gene expression profile. We show that GDNF overexpressing cNPCs expand in vitro, coexpress GFP, and secrete high levels of GDNF protein—before and after differentiation—all qualities advantageous for use as a cell-based approach in feline models of neural degenerative disease.http://dx.doi.org/10.1155/2011/378965
spellingShingle X. Joann You
Ping Gu
Jinmei Wang
Tianran Song
Jing Yang
Chee Gee Liew
Henry Klassen
Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct
Journal of Ophthalmology
title Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct
title_full Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct
title_fullStr Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct
title_full_unstemmed Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct
title_short Efficient Transduction of Feline Neural Progenitor Cells for Delivery of Glial Cell Line-Derived Neurotrophic Factor Using a Feline Immunodeficiency Virus-Based Lentiviral Construct
title_sort efficient transduction of feline neural progenitor cells for delivery of glial cell line derived neurotrophic factor using a feline immunodeficiency virus based lentiviral construct
url http://dx.doi.org/10.1155/2011/378965
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