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Implantation of undifferentiated and pre-differentiated human neural stem cells in the R6/2 transgenic mouse model of Huntington's disease

UNSPECIFIED (2012) Implantation of undifferentiated and pre-differentiated human neural stem cells in the R6/2 transgenic mouse model of Huntington's disease. BMC Neuroscience, 13 (1).

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Abstract

Background: Cell therapy is a potential therapeutic approach for several neurodegenetative disease, including Huntington Disease (HD). To evaluate the putative efficacy of cell therapy in HD, most studies have used excitotoxic animal models with only a few studies having been conducted in genetic animal models. Genetically modified animals should provide a more accurate representation of human HD, as they emulate the genetic basis of its etiology.Results: In this study, we aimed to assess the therapeutic potential of a human striatal neural stem cell line (STROC05) implanted in the R6/2 transgenic mouse model of HD. As DARPP-32 GABAergic output neurons are predominately lost in HD, STROC05 cells were also pre-differentiated using purmorphamine, a hedgehog agonist, to yield a greater number of DARPP-32 cells. A bilateral injection of 4.5x105 cells of either undifferentiated or pre-differentiated DARPP-32 cells, however, did not affect outcome compared to a vehicle control injection. Both survival and neuronal differentiation remained poor with a mean of only 161 and 81 cells surviving in the undifferentiated and differentiated conditions respectively. Only a few cells expressed the neuronal marker Fox3.Conclusions: Although the rapid brain atrophy and short life-span of the R6/2 model constitute adverse conditions to detect potentially delayed treatment effects, significant technical hurdles, such as poor cell survival and differentiation, were also sub-optimal. Further consideration of these aspects is therefore needed in more enduring transgenic HD models to provide a definite assessment of this cell line's therapeutic relevance. However, a combination of treatments is likely needed to affect outcome in transgenic models of HD. © 2012 El Akabawy et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Centers: Other Centers, Institutes, or Units > McGowan Institute for Regenerative Medicine
Date: 9 August 2012
Date Type: Publication
Journal or Publication Title: BMC Neuroscience
Volume: 13
Number: 1
DOI or Unique Handle: 10.1186/1471-2202-13-97
Schools and Programs: School of Medicine > Radiology
Refereed: Yes
Date Deposited: 29 Nov 2016 21:06
Last Modified: 19 Jan 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/29847

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