Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling

Publication date: Available online 12 September 2019Source: Stem Cell ReportsAuthor(s): Soheil Akbari, Gülben Gürhan Sevinç, Nevin Ersoy, Onur Basak, Kubra Kaplan, Kenan Sevinç, Erkin Ozel, Berke Sengun, Eray Enustun, Burcu Ozcimen, Alper Bagriyanik, Nur Arslan, Tamer Tevfik Önder, Esra ErdalSummaryOrganoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner.Graphical Abstract
Source: Stem Cell Reports - Category: Stem Cells Source Type: research