Stem cell transplantation for Huntington's disease.
By way of commentary on a recent report that transplanted adult neural progenitor cells can alleviate functional deficits in a rat lesion model of Huntington's disease [Vazey, E.M., Chen, K., Hughes, S.M., Connor, B., 2006. Transplanted adult neural progenitor cells survive, differentiate and reduce motor function impairment in a rodent model of Huntington's disease. Exp. Neurol. 199, 384-396], we review the current status of the field exploring the use of stem cells, progenitor cells and immortalised cell lines to repair the lesioned striatum in animal models of the human disease. A remarkably rich range of alternative cell types have been used in various animal models, several of which exhibit cell survival and incorporation in the host brain, leading to subsequent functional recovery. In comparing the alternatives with the 'gold standard' currently offered by primary tissue grafts, key issues turn out to be: cell survival, differentiation prior to and following implantation into striatal-like phenotypes, integration and connectivity with the host brain, the nature of the electrophysiological, motor and cognitive tests used to assess functional repair, and the mechanisms by which the grafts exert their function. Although none of the alternatives yet has the capacity to match primary fetal tissues for functional repair, that standard is itself limited, and the long term goal must be not just to match but to surpass present capabilities in order to achieve fully functional reconstruction reliably, flexibly, and on demand.
Dunnett
Stephen B
SB
The Brain Repair Group, School of Biosciences, Cardiff University, Cardiff, Wales, UK. dunnett@cf.ac.uk
Rosser
Anne E
AE
D000818:Animals; D016380:Brain Tissue Transplantation; D002460:Cell Line; D004195:Disease Models, Animal; D006801:Humans; D006816:Huntington Disease / Q000601:surgery / Q000628:therapy*; D017072:Neostriatum / Q000637:transplantation; D033581:Stem Cell Transplantation