Cell
Volume 175, Issue 6, 29 November 2018, Pages 1591-1606.e19
Journal home page for Cell

Article
Long-Term Expansion of Functional Mouse and Human Hepatocytes as 3D Organoids

https://doi.org/10.1016/j.cell.2018.11.013Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Human and mouse hepatocytes can be grown long-term as organoids

  • Hepatocyte organoids consist of progenitors and differentiated hepatocytes

  • Murine hepatocyte organoids reflect regeneration after partial hepatectomy

  • Organoids from primary human hepatocytes engraft into damaged mouse liver

Summary

The mammalian liver possesses a remarkable regenerative ability. Two modes of damage response have been described: (1) The “oval cell” response emanates from the biliary tree when all hepatocytes are affected by chronic liver disease. (2) A massive, proliferative response of mature hepatocytes occurs upon acute liver damage such as partial hepatectomy (PHx). While the oval cell response has been captured in vitro by growing organoids from cholangiocytes, the hepatocyte proliferative response has not been recapitulated in culture. Here, we describe the establishment of a long-term 3D organoid culture system for mouse and human primary hepatocytes. Organoids can be established from single hepatocytes and grown for multiple months, while retaining key morphological, functional and gene expression features. Transcriptional profiles of the organoids resemble those of proliferating hepatocytes after PHx. Human hepatocyte organoids proliferate extensively after engraftment into mice and thus recapitulate the proliferative damage-response of hepatocytes.

Keywords

Human Liver Organoid
Hepatocyte Proliferation
Hepatocyte Organoid
Liver Regeneration

Cited by (0)

11

These authors contributed equally

12

Lead Contact