From Cell Culture to Organoids-Model Systems for Investigating Prion Strain Characteristics

Abstract

Prion diseases are the hallmark protein folding neurodegenerative disease. Their transmissible nature has allowed for the development of many different cellular models of disease where prion propagation and sometimes pathology can be induced. This review examines the range of simple cell cultures to more complex neurospheres, organoid, and organotypic slice cultures that have been used to study prion disease pathogenesis and to test therapeutics. We highlight the advantages and disadvantages of each system, giving special consideration to the importance of strains when choosing a model and when interpreting results, as not all systems propagate all strains, and in some cases, the technique used, or treatment applied, can alter the very strain properties being studied.

Keywords: cell culture; organoids; organotypic slice culture; prion; stem cell; strains.

Figure 1

Organotypic slice culture. Cerebellar (a) and coronal whole-brain (b) organotypic slices from an 8-day-old Tga20 mouse pup; (c–f) Low magnification confocal images of a 56-day-old whole-brain organotypic slice culture, immunostained for neuronal nuclei (NeuN). (c) PrP; (d) astrocytes (GFAP); (e) microglia (Iba1); (f) demonstrating the capability of visualizing different brain regions within a slice; (g) higher magnification image of the cortical region, illustrating the complex in vivo-like cytoarchitecture of organotypic culture with neuronal nuclei in red (NeuN), astrocytes in cyan (GFAP), and microglia in blue (Iba1).