1 Ocak 2019 Dergi makalesi Açık Erişim

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

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    <subfield code="a">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 (&amp;gt;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.</subfield>
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