类有机物
脂肪性肝炎
诱导多能干细胞
生物
细胞生物学
肝星状细胞
纤维化
脂肪变性
炎症
干细胞
脂肪肝
癌症研究
病理
医学
免疫学
胚胎干细胞
内分泌学
疾病
遗传学
基因
作者
Rie Ouchi,Shodai Togo,Masaki Kimura,Tadahiro Shinozawa,Masaru Koido,Hiroyuki Koike,Wendy L. Thompson,Rebekah Karns,Christopher N. Mayhew,Patrick S. McGrath,Heather A. McCauley,Ranran Zhang,Kyle Lewis,Shoyo Hakozaki,Autumn Ferguson,Norikazu Saiki,Yoshimasa Yoneyama,Ichiro Takeuchi,Yo Mabuchi,Chihiro Akazawa,Hiroshi Yoshikawa,James M. Wells,Takanori Takebe
出处
期刊:Cell Metabolism
[Elsevier]
日期:2019-08-01
卷期号:30 (2): 374-384.e6
被引量:290
标识
DOI:10.1016/j.cmet.2019.05.007
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI