Modelling of liver regeneration after hepatectomy
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LETTER TO THE EDITOR, NEWS AND VIEWS
Modelling of liver regeneration after hepatectomy Abdel‑latif Seddek1 · Reham Hassan1 Received: 17 August 2020 / Accepted: 18 August 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Recently, Zafarnia and colleagues published a study on noninvasive imaging and modelling of liver regeneration after partial hepatectomy (Zafarnia et al. 2019). The authors used the well-established experimental procedure, where approximately two-thirds of the livers of mice are removed (Higgins and Anderson 1931; Mitchell and Willenbring 2008). This induces a regeneration process, where functional liver tissue is restored within approximately 7–10 days (Taub 2004; Nishiyama et al. 2015; Michalopoulos 2010). Using non-invasive imaging, the authors quantified the recovery of liver volume (Zafarnia et al. 2019). Moreover, the density of Kupffer cells, infiltrating macrophages and angiogenesis was quantified. Zafarnia et al. observed that normalization of the total liver volume occurred only after 21 days, because transiently (day 8–14), liver volume increased to higher levers as in controls, probably due to edema. The density of tissue resident macrophages (Kupffer cells) did not increase during the regeneration process; in contrast, the overall density of macrophages increased, illustrating the role of macrophages recruited from the blood circulation, an observation that is in agreement with previous studies (Wen et al. 2015; Nishiyama et al. 2015). The angiogenic endothelial cell activity increased at day four and steadily decreased afterwards until day 21. Interestingly, in the mathematical model, angiogenic activity increased in parallel to the macrophage density. In future, it will be interesting to study the influence of specific interventions, e.g. whether blocking of macrophage infiltration into the regenerating liver has an influence on the kinetics of angiogenesis. In recent years, mathematical modelling has been used to gain a better understanding of the mechanisms of liver damage and regeneration (Hoehme et al. 2018, 2017; Ghallab et al. 2016, 2019a; Schließ et al. 2014). For example, spatiotemporal modelling has shown that hepatocytes re-organize * Reham Hassan [email protected] 1
Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt
in the regenerating liver by aligning themselves along the closest microvessel (Hoehme et al. 2010, 2007). Also, bile ducts adapt during liver damage and cholestasis by formation of additional branches to generate a denser ductular mesh at the site of damage (Vartak et al. 2016; Jansen et al. 2017; Leist et al. 2017; Ghallab et al. 2019b; Godoy et al. 2013). However, a major challenge in these studies has been that mice have to be dissected at many periods after an intervention (e.g. hepatectomy). The authors (Zafarnia et al. 2019) are to be congratulated, because they successfully introduced non-invasive imaging techniques, where the same animals can be repeatedly an
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