2. Academic Validation
  3. IL6 supports long-term expansion of hepatocytes in vitro

IL6 supports long-term expansion of hepatocytes in vitro

  • Nat Commun. 2022 Nov 29;13(1):7345. doi: 10.1038/s41467-022-35167-8.
Ren Guo # 1,  Mengmeng Jiang # 1 2 3,  Gang Wang # 4,  Bing Li # 1 3 5,  Xiaohui Jia 1 3,  Yan Ai 1 3 5,  Shanshan Chen 1 3,  Peilan Tang 1 6,  Aijie Liu 1,  Qianting Yuan 1,  Xin Xie 7 8 9 10 11 12
Affiliations

Affiliations

  • 1 State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 2 School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.
  • 3 University of Chinese Academy of Sciences, No.19 A Yuquan Road, 100049, Beijing, China.
  • 4 Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China.
  • 5 School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China.
  • 6 School of Pharmaceutical Science, Nanchang University, Nanchang, 330006, China.
  • 7 State Key Laboratory of Drug Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. xxie@simm.ac.cn.
  • 8 School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China. xxie@simm.ac.cn.
  • 9 University of Chinese Academy of Sciences, No.19 A Yuquan Road, 100049, Beijing, China. xxie@simm.ac.cn.
  • 10 Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 201203, China. xxie@simm.ac.cn.
  • 11 School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, 310024, China. xxie@simm.ac.cn.
  • 12 Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, 264117, Shandong, China. xxie@simm.ac.cn.
  • # Contributed equally.
PMID: 36446858 DOI: 10.1038/s41467-022-35167-8
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.

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