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Human hepatocytes – PXB-cells® – 2020. Part I

Human hepatocytes – PXB-cells® – 2020. Part I

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.

Hata, K. et al. Biomed Res. 2020; 41(1):33. https://pubmed.ncbi.nlm.nih.gov/32092738/

Extracellular apolipoproteins ApoB100 and ApoC3 in PXB-cells, HepG2 and HuH-7 cells

“Lipoprotein profile and lipid metabolism of PXB-cells®, human primary hepatocytes from liver-humanized mice: proposal of novel in vitro system for screening anti-lipidemic drugs”

Hata et al. publication describes lipoprotein profile and lipid metabolism of PXB-cells®, highlighting their suitability to screen anti-lipidemic agents. The paper shows that PXB-cells® mainly release triglycerides and cholesterol as VLDL (like primary human hepatocytes) in contrast to two other hepatoma cell lines, which mainly release LDL. Fenofibrate (PPARα ligand) suppressed lipoprotein production from PXB-cells® in a dose-dependent manner. (VLDL – very low density lipoprotein; LDL – low density lipoprotein).

Three publications below utilized PXB-cells® in HBV research. Please, note that in some cases authors call PXB-cells® “primary human hepatocytes”, without mentioning the trade name (PXB-cells®).

Luo, J. et al. PLoS Pathog. 2020; 16(3): e1008459. https://pubmed.ncbi.nlm.nih.gov/32226051/

 “Role of Hepatitis B virus capsid phosphorylation in nucleocapsid disassembly and covalently closed circular DNA formation”

Luo et al. propose a model whereby rephosphorylation of HBc at both N-terminal domain and C-terminal domain (CTD) by the packaged CDK2 (cyclin-dependent kinase 2), following CTD dephosphorylation during nucleocapsid (NC) maturation, facilitates uncoating and CCC DNA formation by destabilizing mature NCs. (Authors used PXB-cells® for their study)

“… primary human hepatocytes (the PXB-cells), which do not divide in culture, more closely mimic the human hepatocytes in vivo than hepatoma cells, and of HepG2-NTCP cells…”

 

Matsunaga, S. et al. iScience. 2020; 23(3): 100867. https://pubmed.ncbi.nlm.nih.gov/32105634/

“Engineering Cellular Biosensors with Customizable Antiviral Responses Targeting Hepatitis B Virus”

Matsunaga et al. study establishes the concepts of ‘‘engineered immunity’’ where the synNotch (synthetic Notch) platform is utilized for cellular immunotherapy against viral infections. PXB-cells® were used to assess the antiviral activity of the IFNß-HiBiT (interferon ß tagged at their carboxy terminals with the 11-amino-acid luminescent tag HiBiT) produced by α-HBs SNR (anti-HBs synNotch receptor) cells. Reduced HBV DNA in the medium reflected the suppression of viral replication. These results indicate that α-HBs SNR cells can initiate an effective synthetic anti-viral innate immune response following the recognition of HBs antigen. Later, α -HBs SNR cells were incorporated with neutralizing antibody gene. Secreted antibody inhibited preS1 peptide-NTCP interaction and also suppressed HBV infection in PXB cells®.

Chen, S.-W. et al. Sci Rep. 2020; 10(1):14349. https://pubmed.ncbi.nlm.nih.gov/32873852/

“Modulation of hepatitis B virus infection by epidermal growth factor secreted from liver sinusoidal endothelial cells”

Chen et al. used PXB-cells® to study modulation of HBV infection by epidermal growth factor (EGF). With the increase of EGF dose, HBV infection (HBV DNA) initially enhanced in the FBS-free condition. HBV infection gradually reduced with further increase of EGF concentration. (In this publication PXB-cells® are referred as “primary human hepatocytes”).

Finally, the paper below is a nice summary characterizing PXB-cells® and showing long lasting high activity of metabolizing enzymes and transporters. A more detailed summary can be found here:  https://kmthepatech.com/robust-human-hepatocytes-pxb-cells/

Yamasaki, C. et al. PLoS One. 2020; 15(9):e0237809. https://pubmed.ncbi.nlm.nih.gov/32915792/

Morphology of PXB-cells in culture

Yamasaki et al. show the results of the evaluation of human albumin secretion, urea synthesis, cytochrome P450 (CYP) activities, and CYP, UGT, and transporter mRNA expression in PXB-cells® from three different donors. Authors prove PXB-cells® usability and high performance for at least three weeks after isolation. Localization and function of MRP2, NTCP, and BSEP in PXB-cells® was confirmed. It was shown that the high-density cells culture maintained high expressions of some transcriptional factors (HNF4α, PXR, and FXR).

Summary is prepared by Dr. S. Sapelnikova.