4.8 Article

Long-term functional maintenance of primary human hepatocytes in vitro

Journal

SCIENCE
Volume 364, Issue 6438, Pages 399-+

Publisher

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aau7307

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Funding

  1. National Key Research and Development Program of China [2017YFA0103000, 2017YFA0104003, 2016YFA0100103]
  2. National Natural Science Foundation of China [31730059, 31521004, 81670590]
  3. SLS-Qidong Innovation Fund [2016000663]

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The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.

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