Hepatocyte organoids offer PFIC modelling of bile duct damage

Katarína Balážová (Hubrecht Institute, Utrecht, the Netherlands) and colleagues presented their poster describing the use of CRISPR-based genome editing to emulate different PFIC gene alterations in hepatocyte organoids and create a biobank.

“To keep up with the newly identified PFIC subtypes, we need physiologically relevant and flexible disease models,” the researchers explained. “We show that fetal hepatocyte organoids are editable,” they said, adding that these “can thus be used to readily model clinically relevant PFIC mutations.”

CRISPR/Cas9 base editors were used to add a premature STOP codon to induce loss of function of the genes ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, MYO5B, and PLEC, alterations of which are associated with PFIC types 1 to 7, respectively.

Balážová et al noted that the genetically altered organoids have “distinct morphology, ranging from small and dense to large and cystic.”

They also demonstrated that the wild-type hepatocyte organoids have bile canaliculi structures and said that, by introducing a bile acid mix to induce a cholestatic state, future research will be able to “monitor bile uptake, secretion and the structural changes of bile canaliculi associated with cholestasis, serving as an in vitro PFIC model.”