Dataset Information

Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.

ABSTRACT: Human organoid systems recapitulate in vivo organ architecture yet fail to capture complex pathologies such as inflammation and fibrosis. Here, using 11 different healthy and diseased pluripotent stem cell lines, we developed a reproducible method to derive multi-cellular human liver organoids composed of hepatocyte-, stellate-, and Kupffer-like cells that exhibit transcriptomic resemblance to in vivo-derived tissues. Under free fatty acid treatment, organoids, but not reaggregated cocultured spheroids, recapitulated key features of steatohepatitis, including steatosis, inflammation, and fibrosis phenotypes in a successive manner. Interestingly, an organoid-level biophysical readout with atomic force microscopy demonstrated that organoid stiffening reflects the fibrosis severity. Furthermore, organoids from patients with genetic dysfunction of lysosomal acid lipase phenocopied severe steatohepatitis, rescued by FXR agonism-mediated reactive oxygen species suppression. The presented key methodology and preliminary results offer a new approach for studying a personalized basis for inflammation and fibrosis in humans, thus facilitating the discovery of effective treatments.

SUBMITTER: Ouchi R

PROVIDER: S-EPMC6687537 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.

Ouchi Rie R Togo Shodai S Kimura Masaki M Shinozawa Tadahiro T Koido Masaru M Koike Hiroyuki H Thompson Wendy W Karns Rebekah A RA Mayhew Christopher N CN McGrath Patrick S PS McCauley Heather A HA Zhang Ran-Ran RR Lewis Kyle K Hakozaki Shoyo S Ferguson Autumn A Saiki Norikazu N Yoneyama Yosuke Y Takeuchi Ichiro I Mabuchi Yo Y Akazawa Chihiro C Yoshikawa Hiroshi Y HY Wells James M JM Takebe Takanori T

Cell metabolism 20190530 2

Human organoid systems recapitulate in vivo organ architecture yet fail to capture complex pathologies such as inflammation and fibrosis. Here, using 11 different healthy and diseased pluripotent stem cell lines, we developed a reproducible method to derive multi-cellular human liver organoids composed of hepatocyte-, stellate-, and Kupffer-like cells that exhibit transcriptomic resemblance to in vivo-derived tissues. Under free fatty acid treatment, organoids, but not reaggregated cocultured sp ...[more]

PMID: 31155493

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Dataset Information

Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.

Publications

Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids.

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