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Human stem cell-derived astrocytes replicate human prions in a PRNP genotype-dependent manner

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Original languageEnglish
Pages (from-to)3481-3495
JournalJournal of Experimental Medicine
Issue number12
StatePublished - 15 Nov 2017


Prions are infectious agents that cause neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD). The absence of a human cell culture model which replicates human prions has hampered prion disease research for decades. Here we show that astrocytes derived from human induced pluripotent stem cells (iPSC) support the replication of prions from brain samples of CJD patients. For experimental exposure of astrocytes to variant CJD (vCJD), the kinetics of prion replication occur in a prion protein codon 129 genotype-dependent manner, reflecting the genotype-dependent susceptibility to clinical vCJD found in patients. Furthermore, iPSC-derived astrocytes can replicate prions associated with the major sporadic CJD (sCJD) strains found in human patients. Lastly, we demonstrate the sub-passage of prions from infected to naïve astrocyte cultures, indicating the generation of prion infectivity in vitro. Our study addresses a long-standing gap in the repertoire of human prion disease research, providing a new in vitro system for accelerated mechanistic studies and drug discovery.

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  • Journal Article

ID: 44084264