Email updates

Keep up to date with the latest news and content from BMC Neuroscience and BioMed Central.

Open Access Highly Accessed Research article

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

For all author emails, please log on.

Citation and License

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