In our previous post we summarized 2020 publications where PXB-cells® were used in lipid metabolism, drug metabolism and hepatitis B studies. Here we bring to your attention five 2020 publications which discuss the use of PXB-cells® in toxicity-related applications (in 2D and in 3D formats).
Here we summarize 2020 publications where PXB-cells® were used in such application areas as lipid metabolism, drug metabolism and hepatitis B. In Part II we will review 2020 publications where PXB-cells® were used in toxicity-related applications.
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).
January 27, 2021
In vivo OTCD mouse model from PhoenixBio and in vitro model of OTCD based on hepatocytes isolated from those mice were developed by our R&D team.
Our recent Open Access paper “Humanized liver mouse model with transplanted human hepatocytes from patients with ornithine transcarbamylase deficiency” describes the development of a mouse model containing OTC-deficient hepatocytes with the characteristics similar to OTCD patients and in vitro model of OTCD based on hepatocytes isolated from those mice. Ornithine transcarbamylase deficiency (OTCD) is a metabolic and genetic disease which results in the dysfunction of the urea cycle. Primary human hepatocytes isolated from male and female pediatric patients were used for the xenotransplantation into cDNA-uPA/SCID mice to develop this mouse model containing OTC-deficient hepatocytes.
Serial transplantation was used to achieve high repopulation of the mouse liver with donor hepatocytes (Replacement Index of over 80%) from OTC deficient patients. Highly humanized OTCD mice exhibited similar characteristics seen in OTCD patients including increased blood ammonia levels and urine orotic acid levels enhanced by allopurinol.