Human embryonic stem cells rapidly take up and then clear exogenous human and animal prions in vitro

• Published in: The Journal of pathology 2011-04, Vol.223 (5), p.635-645
• Main Authors: Krejciova, Zuzana, Pells, Steve, Cancellotti, Enrico, Freile, Paz, Bishop, Matthew, Samuel, Kay, Robin Barclay, G, Ironside, James W, Manson, Jean C, Turner, Marc L, De Sousa, Paul, Head, Mark W
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; BSE; Cattle; cell culture; Cell Differentiation - physiology; Cells, Cultured; Codons; Creutzfeldt-Jakob disease (CJD); Creutzfeldt-Jakob Syndrome - metabolism; Creutzfeldt-Jakob Syndrome - transmission; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Differentiation; Embryo cells; Embryonic Stem Cells - metabolism; Encephalopathy, Bovine Spongiform - metabolism; Encephalopathy, Bovine Spongiform - transmission; Genotypes; Humans; iatrogenic transmission; Infection; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; mRNA; Neurology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymorphism, Genetic; Prion protein; prion protein (PrP); Prion Proteins; prions; Prions - biosynthesis; Prions - genetics; Prions - pathogenicity; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - genetics; Stem cells; Up-Regulation - physiology
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2832

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.