Cerebral organoids as a new model for prion disease

Human brain has proven difficult to model, and this tissue is not widely available for study. [...]the application of organoid technology to produce 3D cultures of self-patterning brain tissue, human cerebral organoids (hCOs), offers great promise for investigating how brain cells become dysfunctional and die in neurodegenerative conditions. Organoids permit investigation into various aspects of prion disease including (1) different sCJD subtypes; (2) neuronal dysfunction and death; (3) cellular cross-talk; (4) conversion initiating triggers; and (5) efficacy of putative therapeutics. hCO, human cerebral organoid; PrP, prion protein; sCJD, sporadic Creutzfeldt–Jakob disease. https://doi.org/10.1371/journal.ppat.1009747.g001 Organoids become infected with and accumulate human prions Until 2017, no reproducible human cell model of prion infection existed. There was precedent in the literature from mouse models that neural stem cells (NSCs), and mature cultures differentiated from NSCs, would be permissible to infection [1–3]. [...]iPSCs were a prime technology to apply to this problem. Other cells are also involved in maintaining brain health, including microglia and endothelial cells, but these do not originate from the neuroectoderm lineage used to differentiate the neural lineage cells. [...]different approaches are being developed to study these cells.