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

BMC Neuroscience

Research Article

Richard Gale¹  Gillian Bates¹  Saga M Johansson²  Ivan Rattray²  Michel Modo³  Gehan El-Akabawy⁴ 

[1] Department of Medical and Molecular Genetics, Guy’s Hospital, King’s College London School of Medicine, London, SE1 9RT, United Kingdom;Department of Neuroscience, King’s College London, Institute of Psychiatry, SE5 9NU, London, United Kingdom;Department of Neuroscience, King’s College London, Institute of Psychiatry, SE5 9NU, London, United Kingdom;Department of Radiology, McGowan Institute for Regenerative Medicine, University of Pittsburgh, 3025 East Carson St, PA15203, Pittsburgh, USA;Department of Neuroscience, King’s College London, Institute of Psychiatry, SE5 9NU, London, United Kingdom;Faculty of Medicine, Menoufia University, Menoufia, Egypt;

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

DOI  :  10.1186/1471-2202-13-97

 received in 2012-03-13, accepted in 2012-07-24,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundCell 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.ResultsIn 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.ConclusionsAlthough 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.

【 授权许可】

Unknown   
© El Akabawy et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.