IL6 supports long-term expansion of hepatocytes in vitro

Ren Guo, Mengmeng Jiang, Gang Wang, Bing Li, Xiaohui Jia, Yan Ai, Shanshan Chen, Peilan Tang, Aijie Liu, Qianting Yuan and Xin Xie ()
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Ren Guo: Chinese Academy of Sciences
Mengmeng Jiang: Chinese Academy of Sciences
Gang Wang: Fudan University
Bing Li: Chinese Academy of Sciences
Xiaohui Jia: Chinese Academy of Sciences
Yan Ai: Chinese Academy of Sciences
Shanshan Chen: Chinese Academy of Sciences
Peilan Tang: Chinese Academy of Sciences
Aijie Liu: Chinese Academy of Sciences
Qianting Yuan: Chinese Academy of Sciences
Xin Xie: Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Hepatocytes are very difficult to expand in vitro. A few studies have demonstrated that chemical cocktails with growth factors or Wnt ligands can support long-term expansion of hepatocytes via dedifferentiation. However, the culture conditions are complex, and clonal expansion of hepatic progenitors with full differentiation capacity are rarely reported. Here, we discover IL6, combined with EGF and HGF, promotes long-term expansion (>30 passages in ~150 days with theoretical expansion of ~1035 times) of primary mouse hepatocytes in vitro in simple 2D culture, by converting hepatocytes into induced hepatic progenitor cells (iHPCs), which maintain the capacity of differentiation into hepatocytes. IL6 also supports the establishment of single hepatocyte-derived iHPC clones. The summation of the downstream STAT3, ERK and AKT pathways induces a number of transcription factors which support rapid growth. This physiological and simple way may provide ideas for culturing previously difficult-to-culture cell types and support their future applications.

Date: 2022
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DOI: 10.1038/s41467-022-35167-8

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