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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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{
  "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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