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Founder cells for hepatocytes during liver regeneration: from identification to application

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Abstract

Liver regeneration (LR) capacity in vertebrates developed through natural selection over a hundred million years of evolution. To maintain homeostasis or recover from various injuries, liver cells must regenerate; this process includes the renewal of parenchymal and nonparenchymal cells as well as the formation of liver structures. The cellular origin of newly grown tissue is one of the critical questions in this area and has been a subject of prolonged debate. The regenerative tissue may derive from either hepatocyte self-duplication or liver stem/progenitor cells (LSPCs). Recently, hepatocyte subpopulations and cholangiocytes were also described as important founder cells. The niche that triggers the proliferation of hepatocytes and the differentiation of LSPCs has been extensively studied. Meanwhile, in vitro culture systems for liver founder cells and organoids have been developed rapidly for mechanistic studies and potential therapeutic purposes. This review summarizes the cellular sources and niches that give rise to renewed hepatocytes during LR, and it also describes in vitro culture studies of those founder cells for future applications, as well as current reports for stem cell-based therapies for liver diseases.

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Acknowledgements

This article was supported by grants from the Zhejiang Provincial Natural Science Foundation of China (No. LQ19C050004 and LY19H200004) and the National Natural Science Foundation of China (No. 81772546). We thank Dr. Xiangwei Gao for the critical reading of the manuscript.

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  1. Key Laboratory of Endoscopic Technique Research of Zhejiang Province, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China

    Saisai Wei, Jiacheng Tang & Xiujun Cai

  2. Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China

    Xiujun Cai

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  1. Saisai Wei
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Wei, S., Tang, J. & Cai, X. Founder cells for hepatocytes during liver regeneration: from identification to application. Cell. Mol. Life Sci. 77, 2887–2898 (2020). https://doi.org/10.1007/s00018-020-03457-3

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