These authors contributed equally to this study.
Human embryonic stem cells rapidly take up and then clear exogenous human and animal prions in vitro†
Article first published online: 21 FEB 2011
Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 223, Issue 5, pages 635–645, April 2011
How to Cite
Krejciova, Z., Pells, S., Cancellotti, E., Freile, P., Bishop, M., Samuel, K., Robin Barclay, G., Ironside, J. W., Manson, J. C., Turner, M. L., De Sousa, P. and Head, M. W. (2011), Human embryonic stem cells rapidly take up and then clear exogenous human and animal prions in vitro. J. Pathol., 223: 635–645. doi: 10.1002/path.2832
Dr Paul De Sousa is Chief Scientific Officer of Roslin Cells Ltd. The remaining authors have no conflicts of interest to declare.
- Issue published online: 10 MAR 2011
- Article first published online: 21 FEB 2011
- Accepted manuscript online: 26 NOV 2010 06:50AM EST
- Manuscript Accepted: 16 NOV 2010
- Manuscript Revised: 15 NOV 2010
- Manuscript Received: 10 AUG 2010
- stem cells;
- Creutzfeldt–Jakob disease (CJD);
- prion protein (PrP);
- cell culture;
- iatrogenic transmission
Susceptibility to prion infection involves interplay between the prion strain and host genetics, but expression of the host-encoded cellular prion protein is a known prerequisite. Here we consider human embryonic stem cell (hESC) susceptibility by characterizing the genetics and expression of the normal cellular prion protein and by examining their response to acute prion exposure. Seven hESC lines were tested for their prion protein gene codon 129 genotype and this was found to broadly reflect that of the normal population. hESCs expressed prion protein mRNA, but only low levels of prion protein accumulated in self-renewing populations. Following undirected differentiation, up-regulation of prion protein expression occurred in each of the major embryonic lineages. Self-renewing populations of hESCs were challenged with infectious human and animal prions. The exposed cells rapidly and extensively took up this material, but when the infectious source was removed the level and extent of intracellular disease-associated prion protein fell rapidly. In the absence of a sufficiently sensitive test for prions to screen therapeutic cells, and given the continued use of poorly characterized human and animal bioproducts during hESC derivation and cultivation, the finding that hESCs rapidly take up and process abnormal prion protein is provocative and merits further investigation. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.