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Self‐assembled liver organoids recapitulate hepatobiliary organogenesis in vitro
Author(s) -
Vyas Dipen,
Baptista Pedro M.,
Brovold Matthew,
Moran Emma,
Gaston Brandon,
Booth Chris,
Samuel Michael,
Atala Anthony,
Soker Shay
Publication year - 2018
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.29483
Subject(s) - organoid , organogenesis , in vitro , microbiology and biotechnology , biology , chemistry , biochemistry , gene
Several three‐dimensional cell culture systems are currently available to create liver organoids. In gneral, these systems display better physiologic and metabolic aspects of intact liver tissue compared with two‐dimensional culture systems. However, none reliably mimic human liver development, including parallel formation of hepatocyte and cholangiocyte anatomical structures. Here, we show that human fetal liver progenitor cells self‐assembled inside acellular liver extracellular matrix scaffolds to form three‐dimensional liver organoids that recapitulated several aspects of hepatobiliary organogenesis and resulted in concomitant formation of progressively more differentiated hepatocytes and bile duct structures. The duct morphogenesis process was interrupted by inhibiting Notch signaling, in an attempt to create a liver developmental disease model with a similar phenotype to Alagille syndrome. Conclusion : In the current study, we created an in vitro model of human liver development and disease, physiology, and metabolism, supported by liver extracellular matrix substrata; we envision that it will be used in the future to study mechanisms of hepatic and biliary development and for disease modeling and drug screening. (H epatology 2018;67:750‐761).