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

TitleHuman embryonic stem cells rapidly take up and then clear exogenous human and animal prions in vitro.
Publication TypeJournal Article
Year of Publication2011
AuthorsKrejciova Z, Pells S, Cancellotti E, Freile P, Bishop M, Samuel K, Barclay GR, Ironside JW, Manson JC, Turner ML, de Sousa P, Head MW
JournalJ Pathol
Date Published2011 Apr
KeywordsAnimals, Cattle, Cell Differentiation, Cells, Cultured, Creutzfeldt-Jakob Syndrome, Embryonic Stem Cells, Encephalopathy, Bovine Spongiform, Humans, Polymorphism, Genetic, Prions, Reverse Transcriptase Polymerase Chain Reaction, RNA, Messenger, Up-Regulation

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.

Alternate JournalJ. Pathol.
PubMed ID21341268
Grant ListCZB/4/588 / / Chief Scientist Office / United Kingdom
G0300484 / / Medical Research Council / United Kingdom
G0900580 / / Medical Research Council / United Kingdom
/ / Department of Health / United Kingdom