Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate- and hydrogen peroxide-mediated death of staurosporine-differentiated RGC-5 cells

Matthew M Harper; Laura Adamson; Bas Blits; Mary Bartlett Bunge; Sinisa D Grozdanic; Donald S Sakaguchi

doi:10.1016/j.exer.2009.05.013

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Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate- and hydrogen peroxide-mediated death of staurosporine-differentiated RGC-5 cells

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Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate- and hydrogen peroxide-mediated death of staurosporine-differentiated RGC-5 cells

Matthew M Harper, Laura Adamson, Bas Blits, Mary Bartlett Bunge, Sinisa D Grozdanic and Donald S Sakaguchi

Experimental Eye Research, Vol.89(4), pp.538-548

10/2009

DOI: 10.1016/j.exer.2009.05.013

PMCID: PMC2743788

PMID: 19524566

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Abstract

The purpose of this study was to determine the viability of cell-based delivery of brain-derived neurotrophic factor (BDNF) from genetically modified mesenchymal stem cells (MSCs) for neuroprotection of RGC-5 cells. RGC-5 cells were differentiated with the protein kinase inhibitor staurosporine (SS) and exposed to the cellular stressors glutamate or H2O2. As a neuroprotective strategy, these cells were then co-cultured across a membrane insert with mesenchymal stem cells (MSCs) engineered with a lentiviral vector for production of BDNF (BDNF-MSCs). As a positive control, recombinant human BDNF (rhBDNF) was added to stressed RGC-5 cells. After SS-differentiation RGC-5s developed neuronal-like morphologies, and a significant increase in the proportion of RGC-5s immunoreactive for TuJ-1 and Brn3a was observed. Differentiated RGC-5s also had prominent TrkB staining, demonstrating expression of the high-affinity BDNF receptor. Treatment of SS-differentiated RGC-5s with glutamate or H2O2, produced significant cell death (56.0 ± 7.02 and 48.90 ± 4.58% of control cells, respectively) compared to carrier-solution treated cells. BDNF-delivery from MSCs preserved more RGC-5 cells after treatment with glutamate (80.0 ± 5.40% cells remaining) than control GFP expressing MSCs (GFP-MSCs, 57.29 ± 1.89%, p < 0.01). BDNF-MSCs also protected more RGC-5s after treatment with H2O2 (65.6 ± 3.47%) than GFP-MSCs (46.0 ± 4.20%, p < 0.01). We have shown survival of differentiated RGC-5s is reduced by the cellular stressors glutamate and H2O2. Additionally, our results demonstrate that genetically modified BDNF-producing MSCs can enhance survival of stressed RGC-5 cells and therefore, may be effective vehicles to deliver BDNF to retinal ganglion cells affected by disease.

RGC-5

BDNF

ganglion cells

neuroprotection

mesenchymal stem cells

glaucoma

Details

Title: Subtitle: Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate- and hydrogen peroxide-mediated death of staurosporine-differentiated RGC-5 cells
Creators: Matthew M Harper - Iowa State University, Ames, IA 50011, USA
Laura Adamson - Iowa State University, Ames, IA 50011, USA
Bas Blits - Netherlands Institute for Brain Research, Amsterdam, The Netherlands
Mary Bartlett Bunge - Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL, USA
Sinisa D Grozdanic - Iowa State University, Ames, IA 50011, USA
Donald S Sakaguchi - Iowa State University, Ames, IA 50011, USA
Resource Type: Journal article
Publication Details: Experimental Eye Research, Vol.89(4), pp.538-548
DOI: 10.1016/j.exer.2009.05.013
PMID: 19524566
PMCID: PMC2743788
NLM abbreviation: Exp Eye Res
ISSN: 0014-4835
eISSN: 1096-0007
Publisher: Elsevier Ltd
Language: English
Date published: 10/2009
Academic Unit: Biology; Ophthalmology and Visual Sciences
Record Identifier: 9983980281402771

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