Engrafted human stem cell–derived hepatocytes establish an infectious HCV murine model

Carpentier, Arnaud; Tesfaye, Abeba; Chu, V.; Nimgaonkar, Ila; Zhang, Fang; Lee, Seung Bum; Thorgeirsson, Snorri S.; Feinstone, Stephen M.; Liang, T. Jake

doi:10.1172/jci75456

Cited by 128 publications

(155 citation statements)

References 65 publications

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“…We adapted a recently published protocol that described the derivation of functional hepatocyte-like cells from human embryonic stem cells (ESCs) and iPSCs. 27,28 Although the kinetics of hepatic differentiation of RhiPSCs was similar to that of human iPSCs, we found that hypoxic culture (5% O 2 ) during definitive endoderm induction was necessary in RhiPSC differentiation ( Figure S7). After 4 days of differentiation, pluripotent genes were downregulated and RhiPSCs generated homogeneous definitive endoderm, which expressed SOX17 and FOXA2.…”

Section: Endodermal Differentiation From Edited Rhipscsmentioning

confidence: 86%

“…After 4 days, cells were transferred to a normoxic incubator and further differentiated to hepatoblasts in medium with 100 ng/ml hepatocyte growth factor and 1% DMSO for 8 days, as previously described. 27,28 Finally, cells were pushed toward hepatocyte-like cells with the addition of 10 À7 M dexamethasone for 3 additional days. At each time point, cells were analyzed by Taqman RT-qPCR and immunostaining as previously described.…”

Section: Hepatic Differentiationmentioning

confidence: 99%

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Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of Transgenes in Differentiated Cells of All Germ Layers

et al. 2017

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Section: Endodermal Differentiation From Edited Rhipscsmentioning

confidence: 86%

Section: Hepatic Differentiationmentioning

confidence: 99%

Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of Transgenes in Differentiated Cells of All Germ Layers

et al. 2017

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“…126–130 The ability of transplanted cells to functionally repopulate livers of immune-deficient mice is the standard to establish that they are hepatocytes, rather than cells with hepatocyte-like features, which are unable to repopulate livers. To date, only limited repopulation of human HLCs has been reported 69,131–134…”

Section: Required Functions Of Adult Hepatocytesmentioning

confidence: 99%

Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells

et al. 2018

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The incidence of liver disease is increasing globally. The only curative therapy for severe end-stage liver disease, liver transplantation, is limited by the shortage of organ donors. In vitro models of liver physiology have been developed and new technologies and approaches are progressing rapidly. Stem cells might be used as a source of liver tissue for development of models, therapies, and tissue-engineering applications. However, we have been unable to generate and maintain stable and mature adult liver cells ex vivo. We review factors that promote hepatocyte differentiation and maturation, including growth factors, transcription factors, microRNAs, small molecules, and the microenvironment. We discuss how the hepatic circulation, microbiome, and nutrition affect liver function, and the criteria for considering cells derived from stem cells to be fully mature hepatocytes. We explain the challenges to cell transplantation and consider future technologies for use in hepatic stem cell maturation, including 3-dimensional biofabrication and genome modification.

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“…HLCs do not engraft efficiently in most xenorecipient models possibly due to their incomplete differentiation phenotype. However, recently it was shown that transplantation of HLCs into immunodeficient MUP-uPA mice yielded a sufficiently high hepatic chimerism to support hepatitis C virus infection [32]. While these results require independent confirmation, this system holds promise for systematically analyzing the impact of host polymorphisms on HBV and HDV infections in mice engrafted with patient-specific hepatocytes.…”

Section: Host Adaptation: Xenotransplantation Modelsmentioning

confidence: 99%

Determinants of hepatitis B and delta virus host tropism

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Ploß

2015

Current Opinion in Virology

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Hepatitis B virus (HBV) infections are a global health problem afflicting approximately 360 million patients. Of these individuals, 15–20 million are co-infected with hepatitis delta virus (HDV). Progress towards curative therapies has been impeded by the highly restricted host tropism of HBV, which is limited to productive infections in humans and chimpanzees. Here, we will discuss different approaches that have been taken to study HBV and HDV infections in vivo. The development of transgenic and humanized mice has lead to deeper insights into HBV pathogenesis. An improved understanding of the determinants governing HBV and HDV species tropism will aid the construction of a small animal model with inheritable susceptible to HBV/HDV.

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Engrafted human stem cell–derived hepatocytes establish an infectious HCV murine model

Cited by 128 publications

References 65 publications

Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of Transgenes in Differentiated Cells of All Germ Layers

Rhesus iPSC Safe Harbor Gene-Editing Platform for Stable Expression of Transgenes in Differentiated Cells of All Germ Layers

Biotechnology Challenges to In Vitro Maturation of Hepatic Stem Cells

Determinants of hepatitis B and delta virus host tropism

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