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. 2021 Oct 18;53(10):1512–1528. doi: 10.1038/s12276-021-00579-x

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a Preclinical hepatocyte transplantation studies are typically performed in mice with inducible hepatocyte-specific liver injury to evaluate the in vivo regenerative capacity of in vitro-expanded hepatocytes. In this setting, the regeneration of host hepatocytes is impaired, giving donor cells a proliferative advantage. b Transplantation of cultured murine hepatocytes in Fah^−/− mice results in repopulation of the host liver parenchyma by donor cells. Left panel: Transplanted murine hepatocyte organoids gave rise to grafts of various sizes, as shown by immunostaining of FAH. Right panels: upon transplantation of hepatocytes isolated from doxycycline-treated Axin2-rtTA;TetO-H2B:GFP reporter mice, GFP⁺ cells could be observed in donor cell grafts by immunofluorescent imaging. Upper panel: smaller grafts showed scattered GFP⁺ donor cells. Bottom panel: Larger grafts showed GFP⁺ cells at the graft-host tissue boundary only. Scale bars: 100 µm. Images adapted from Peng et al. 2018²⁵. c Crosstalk between donor hepatocytes, host hepatocytes, and other cell types in the injured host liver microenvironment facilitates donor cell repopulation. Potential factors that contribute to donor cell repopulation in the host liver, based on hepatocyte transplantation studies^25,144–147 (indicated by ^*) and liver regeneration studies^53,60,63,142 (^†), are listed in the lower panel. ANG: angiopoietin; HSC: hepatic stellate cell; EC: endothelial cell.