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Non-alcoholic fatty liver-like properties of PXB-cells

Non-alcoholic fatty liver-like properties of PXB-cells

February 4, 2021

The recently published Letter to Editor (“PXB-cells, fresh primary hepatocytes from humanized mouse livers, exhibit nonalcoholic fatty liver like properties, including large very low-density lipoproteins”, J. Biol. Micromol., 2021; 21 (1), 51-52) investigated intra- and extracellular lipid levels and lipoprotein profiles in PXB-cells® isolated at several time points post-transplantation of human hepatocytes into the PXB-mouse®. Numerous large lipid droplets were found in PXB-cells isolated 16- and 19-weeks post-transplantion of human hepatocytes into PXB-mice. This may occur due to a deficiency in circulating human growth factor in the PXB-Mouse®, as was previously described in “Growth Hormone-Dependent Pathogenesis of Human Hepatic Steatosis in a Novel Mouse Model Bearing a Human Hepatocyte-Repopulated Liver” by Dr. C. Tateno and her team (Endocrinology, 2011; 152: 1479-1491).

Figure 1. Preparation of PXB-cells from urokinase-type plasminogen activator/severe combined immunodeficiency (uPA/SCID) mice with humanized livers (PXB-mouse).

Intra- and extracellular lipid levels (cholesterol and triglycerides) were measured at 5-, 16- and 19-weeks post transplantion (see Table with an example of 5-, 16- and 19-weeks measurement). Intracellular triglyceride levels markedly increased with longer post-transplantation durations; however, extracellular triglyceride levels did not show such a significant increase. The particle size of very low-density lipoproteins (VLDL) released from PXB-cells was evaluated and it was shown that their size increased with the increase of time post transplantation of human hepatocytes into PXB-mice. The authors suggest that the increase in the size of VLDL has a potential to serve as a minimally invasive plasma biomarker for the diagnosis and/or progression of non-alcoholic fatty liver disease (NAFLD).

Table 1. Intra- and extracellular lipid contents in NAFL-like PXB-cells

Table 1. Intra- and extracellular lipid contents in NAFL-like PXB-cells

*Data represent means ± standard deviations (n=3). P<0.05 vs 5W.

The summary of the publication was prepared by S. Sapelnikova.