NR AXIA
AU Andre,R.; Sutton,L.M.; Miljan,E.; Sinden,J.D.; Collinge,J.; Tabrizi,S.J.
TI Towards the Development of a Neural Stem Cell Model of Human Prion Disease
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.170
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Introduction: To date, most prion research has been undertaken using animal models. However, modelling prion disease using cell culture has proven more difficult. Prion susceptible cell lines do exist, but are limited to the propagation of either mouseadapted or sheep scrapie prions. There are currently no reported cell lines able to stably propagate human prions. The development of such a cell line remains key to better understanding the cellular and molecular basis of human prion disease, the development of anti-prion therapeutics and to establish diagnostic assays for prion screening. We are currently developing a unique model of human vCJD using differentiated human neural stem cells.
Aim: To develop a cell line able to stably propagate human prions associated with vCJD.
Methods: Human neural stem cells were derived from 10-week foetal ventral mesencephalon and immortalised by overexpression of the v-myc oncogene. They expand indefinitely in culture as stem cells, but upon removal of key growth factors, differentiate predominantly to a stable, mature neuronal phenotype. Anti-PrP antibodies and metabolic labelling were then used to provide evidence of de novo PrPsc production in these cells following exposure to vCJD prions.
Results: The human neural stem cells used differentiate into stable cultures of neuronal cells with a strong phenotypic resemblance to primary neurones in the human brain. Furthermore, they express increased levels of PrPc. This makes them a promising candidate for modelling the propagation of human prions. Undifferentiated cells are not able to propagate prions. However, preliminary data will be presented on the susceptibility of differentiated cultures to human prions and their ability to produce de novo PrPsc. On-going work is being undertaken to characterise these cells more fully.
Conclusion: Taken together, the data suggest that differentiated human neural stem cells appear able to stably propagate human prions. Successfully developing such a model should provide a better understanding of the cellular pathophysiology of human prion disease.
AD R. Andre, L. Sutton, J. Collinge, S. Tabrizi, UCL Institute of Neurology, National Hospital for Neurology and Neurosurgery, Queen Square, MRC Prion Unit, Dept of Neurodegenerative Disease, UK; E. Miljan, J. Sinden, ReNeuron Group plc, Surrey Research Park, UK
SP englisch
PO Schottland
EA pdf-Datei und Poster (Posterautoren ergänzt um J.E. Podesta und P.C. Klöhn)