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A Millifluidic Perfusion Cassette for Studying the Pathogenesis of Enteric Infections Using Ex-Vivo Organoids
Ist Teil von
Annals of biomedical engineering, 2021-04, Vol.49 (4), p.1233-1244
Ort / Verlag
Cham: Springer International Publishing
Erscheinungsjahr
2021
Quelle
MEDLINE
Beschreibungen/Notizen
To generate physiologically-relevant experimental models, the study of enteric diarrheal diseases is turning increasingly to advanced
in vitro
models that combine
ex vivo
, stem cell-derived “organoid” cell lines with bioengineered culture environments that expose them to mechanical stimuli, such as fluid flow. However, such approaches require considerable technical expertise with both microfabrication and organoid culture, and are, therefore, inaccessible to many researchers. For this reason, we have developed a perfusion system that is simple to fabricate, operate, and maintain. Its dimensions approximate the volume and cell culture area of traditional 96-well plates and allow the incorporation of fastidious primary, stem cell-derived cell lines with only minimal adaptation of their established culture techniques. We show that infections with enteroaggregative
E. coli
and norovirus, common causes of infectious diarrhea, in the system display important differences from static models, and in some ways better recreate the pathophysiology of
in vivo
infections. Furthermore, commensal strains of bacteria can be added alongside the pathogens to simulate the effects of a host microbiome on the infectious process. For these reasons, we believe that this perfusion system is a powerful, yet easily accessible tool for studying host-pathogen interactions in the human intestine.