title: Implantation of undifferentiated and pre-differentiated human neural stem cells in the R6/2 transgenic mouse model of Huntington's disease.
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.
authors.affiliation: Department of Neuroscience, King's College London, Institute of Psychiatry, London, SE5 9NU, United Kingdom.
authors.forename: Gehan
authors.initials: G
authors.lastname: El-Akabawy
authors.forename: Ivan
authors.initials: I
authors.lastname: Rattray
authors.forename: Saga M
authors.initials: SM
authors.lastname: Johansson
authors.forename: Richard
authors.initials: R
authors.lastname: Gale
authors.forename: Gillian
authors.initials: G
authors.lastname: Bates
authors.forename: Michel
authors.initials: M
authors.lastname: Modo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001526:Behavioral Symptoms / Q000209:etiology / Q000601:surgery; D001835:Body Weight / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003342:Corpus Striatum / Q000166:cytology / Q000196:embryology; D004195:Disease Models, Animal; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005333:Fetus; D018737:Hand Strength / Q000502:physiology; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*; D045442:Rotarod Performance Test; D014162:Transfection; D018911:Trinucleotide Repeats / Q000235:genetics
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C496506:Foxa3 protein, mouse; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D051543:Hepatocyte Nuclear Factor 3-gamma