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

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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    "creators": [
      {
        "name": "Akbari, Soheil"
      }, 
      {
        "affiliation": "Koc Univ, Fac Med, TR-34450 Istanbul, Turkey", 
        "name": "Sevinc, Gulben Gurhan"
      }, 
      {
        "affiliation": "Dokuz Eylul Univ, Hlth Sci Inst, Dept Histol & Embryol, TR-35340 Izmir, Turkey", 
        "name": "Ersoy, Nevin"
      }, 
      {
        "name": "Basak, Onur"
      }, 
      {
        "name": "Kaplan, Kubra"
      }, 
      {
        "affiliation": "Koc Univ, Fac Med, TR-34450 Istanbul, Turkey", 
        "name": "Sevinc, Kenan"
      }, 
      {
        "affiliation": "Koc Univ, Fac Med, TR-34450 Istanbul, Turkey", 
        "name": "Ozel, Erkin"
      }, 
      {
        "affiliation": "Koc Univ, Fac Med, TR-34450 Istanbul, Turkey", 
        "name": "Sengun, Berke"
      }, 
      {
        "affiliation": "Koc Univ, Fac Med, TR-34450 Istanbul, Turkey", 
        "name": "Enustun, Eray"
      }, 
      {
        "affiliation": "Koc Univ, Fac Med, TR-34450 Istanbul, Turkey", 
        "name": "Ozcimen, Burcu"
      }, 
      {
        "name": "Bagriyanik, Alper"
      }, 
      {
        "name": "Arslan, Nur"
      }, 
      {
        "affiliation": "Koc Univ, Fac Med, TR-34450 Istanbul, Turkey", 
        "name": "Onder, Tamer Tevfik"
      }, 
      {
        "name": "Erdal, Esra"
      }
    ], 
    "description": "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.", 
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      "issue": "4", 
      "pages": "627-641", 
      "title": "STEM CELL REPORTS", 
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      "id": "cc-by"
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    "title": "Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling"
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