Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling
STEM CELL REPORTS, cilt.13, sa.4, ss.627-641, 2019 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 13 Sayı: 4
- Basım Tarihi: 2019
- Doi Numarası: 10.1016/j.stemcr.2019.08.007
- Dergi Adı: STEM CELL REPORTS
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
- Sayfa Sayıları: ss.627-641
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Hacettepe Üniversitesi Adresli: Hayır
Özet
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.