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Akbari, Soheil; Sevinc, Gulben Gurhan; Ersoy, Nevin; Basak, Onur; Kaplan, Kubra; Sevinc, Kenan; Ozel, Erkin; Sengun, Berke; Enustun, Eray; Ozcimen, Burcu; Bagriyanik, Alper; Arslan, Nur; Onder, Tamer Tevfik; Erdal, Esra
{ "DOI": "10.1016/j.stemcr.2019.08.007", "abstract": "Organoid 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 (ASST) 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.", "author": [ { "family": "Akbari", "given": " Soheil" }, { "family": "Sevinc", "given": " Gulben Gurhan" }, { "family": "Ersoy", "given": " Nevin" }, { "family": "Basak", "given": " Onur" }, { "family": "Kaplan", "given": " Kubra" }, { "family": "Sevinc", "given": " Kenan" }, { "family": "Ozel", "given": " Erkin" }, { "family": "Sengun", "given": " Berke" }, { "family": "Enustun", "given": " Eray" }, { "family": "Ozcimen", "given": " Burcu" }, { "family": "Bagriyanik", "given": " Alper" }, { "family": "Arslan", "given": " Nur" }, { "family": "Onder", "given": " Tamer Tevfik" }, { "family": "Erdal", "given": " Esra" } ], "container_title": "STEM CELL REPORTS", "id": "75351", "issue": "4", "issued": { "date-parts": [ [ 2019, 1, 1 ] ] }, "page": "627-641", "title": "Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling", "type": "article-journal", "volume": "13" }
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