Generation of hepatobiliary organoids from human induced pluripotent stem cells

• DOI: 10.1016/j.jhep.2018.12.028
• Publication Date: 2019-01-09T00:44:02Z
• Authors: Fenfang Wu; Di Wu; Yong Ren; Yuhua Huang; Bo Feng; Nan Zhao; Taotao Zhang; Xiaoni Chen; Shangwu Chen; Anlong Xu
• Keywords: Organoid

Highlights•We established a system to generate hiPSC-derived hepatobiliary organoids in vitro.•To varying degrees, this model recapitulated several key aspects of organogenesis.•The displayed series hepatic and biliary functional attributes.•This does not rely on any exogenous cells or genetic manipulation.Graphical abstractAbstractBackground & AimsHuman induced pluripotent stem cell (hiPSC)-derived liver modeling systems have the potential overcome shortage donors for clinical application become drug development. Although strategies are available micro-tissues, few succeeded generating organoid with structure from hiPSCs.MethodsAt differentiation stages I II (day 1–15), 25% mTeSR™ culture medium was added induce endodermal mesodermal commitment thereafter co-differentiation. At stage III 15–45), 10% cholesterol+ MIX maturation promote formation organoids. Phenotypes functions were determined by specific markers multiple assays both vitro vivo.ResultsIn system, hiPSCs form 3D some extent early hepatogenesis parallel fashion. The attributes. Specifically, hepatocyte-like could take up indocyanine green, accumulate lipid glycogen, appropriate secretion ability (albumin urea) metabolic (CYP3A4 activity inducibility); structures showed gamma glutamyltransferase efflux rhodamine store bile acids. Furthermore, after transplantation into immune-deficient mice, survived more than 8 weeks.ConclusionThis is first time that been generated hiPSCs. will be useful studies molecular mechanisms development has important therapy diseases.Lay summaryHerein, we human cell-derived vitro, without manipulation. To able recapitulate organogenesis fashion, holding great promise transplantation.