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

• Published in: Cellular and molecular life sciences : CMLS Vol. 77; no. 15; pp. 2887 - 2898
• Main Authors: Wei, Saisai, Tang, Jiacheng, Cai, Xiujun
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2020; Springer Nature B.V
• Subjects: Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell culture; Cell Differentiation; Cell proliferation; Cell- and Tissue-Based Therapy; Cellular structure; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - therapy; Hepatic Stellate Cells - cytology; Hepatic Stellate Cells - metabolism; Hepatic Stellate Cells - transplantation; Hepatocytes; Hepatocytes - cytology; Hepatocytes - metabolism; Hepatocytes - transplantation; Homeostasis; Humans; Life Sciences; Liver; Liver diseases; liver regeneration; Liver Regeneration - physiology; Natural selection; Organoids; Progenitor cells; Regeneration; Review; Stem cells; Stem Cells - cytology; Stem Cells - metabolism; Subpopulations; Therapeutic applications; therapeutics; Vertebrates; Cellular origin; Niche; Organoid; Liver stem/progenitor cell; Stem cell therapy; Liver regeneration
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-020-03457-3

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.