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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

Gehan El-Akabawy12, Ivan Rattray1, Saga M Johansson1, Richard Gale3, Gillian Bates3 and Michel Modo14*

Author Affiliations

1 Department of Neuroscience, King’s College London, Institute of Psychiatry, London, SE5 9NU, United Kingdom

2 Menoufia University, Faculty of Medicine, Menoufia, Egypt

3 Department of Medical and Molecular Genetics, Guy’s Hospital, King’s College London School of Medicine, London, SE1 9RT, United Kingdom

4 Department of Radiology, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 3025 East Carson St, Pittsburgh, PA15203, USA

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BMC Neuroscience 2012, 13:97  doi:10.1186/1471-2202-13-97

Published: 9 August 2012



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.


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.


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.

Neural stem cells; Human; Cell therapy; R6/2; Pre-differentiated cells; DARPP-32; Striatum; Purmorphamine; Huntington’s disease; Behaviour; MRI; Cell survival