Yayınlanmış 1 Ocak 2019
| Sürüm v1
Dergi makalesi
Açık
Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling
Oluşturanlar
- 1. Koc Univ, Fac Med, TR-34450 Istanbul, Turkey
- 2. Dokuz Eylul Univ, Hlth Sci Inst, Dept Histol & Embryol, TR-35340 Izmir, Turkey
Açıklama
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.
Dosyalar
bib-2c3ac97b-6b43-44fc-b482-afbf10a34f73.txt
Dosyalar
(296 Bytes)
| Ad | Boyut | Hepisini indir |
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md5:bef3640ef645caeb93fc0fcf919f2410
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296 Bytes | Ön İzleme İndir |