Blood Monocyte-Derived Neohepatocytes as in Vitro Test System for Drug Metabolism

@article{Ehnert2008BloodMN,
  title={Blood Monocyte-Derived Neohepatocytes as in Vitro Test System for Drug Metabolism},
  author={Sabrina Ehnert and Andreas K. Nussler and A. Lehmann and Steven Dooley},
  journal={Drug Metabolism and Disposition},
  year={2008},
  volume={36},
  pages={1922 - 1929}
}
The gold standard for human drug metabolism studies is primary hepatocytes. However, availability is limited by donor organ scarcity. Therefore, efforts have been made to provide alternatives, e.g., the hepatocyte-like (NeoHep) cell type, which was generated from peripheral blood monocytes. In this study, expression and activity of phase I and phase II drug-metabolizing enzymes were investigated during transdifferentiation of NeoHep cells and compared with primary human hepatocytes. Important… 

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References

SHOWING 1-10 OF 47 REFERENCES
Human Monocyte-Derived Neohepatocytes: A Promising Alternative to Primary Human Hepatocytes for Autologous Cell Therapy
TLDR
These data convincingly show that NeoHep cells display a phenotype and specific in vitro metabolic functions that are quantitatively and qualitatively comparable in part with those of primary human hepatocytes, and could be clinically applied in an autologous setting for the treatment of end-stage liver diseases or for improving liver function in patients who have undergone critical liver-mass resection.
Cytochrome P450 expression in human hepatocytes and hepatoma cell lines: molecular mechanisms that determine lower expression in cultured cells
TLDR
The loss of biotransformation activity in cultured hepatic cells is caused by a decrease in CYP transcription, which correlates with an alteration in the expression of key transcription factors.
Cell lines: a tool for in vitro drug metabolism studies.
TLDR
Cell line models developed and successfully used in drug metabolism testing to generate metabolically competent immortalized hepatocytes and new strategies have been explored to upregulate the expression of drug-metabolizing enzymes in cell lines of a human origin.
Drug metabolism in hepatocyte sandwich cultures of rats and humans.
Comparison of primary human hepatocytes and hepatoma cell line Hepg2 with regard to their biotransformation properties.
TLDR
Human hepatocytes are the preferred model for biotransformation in human liver, whereas HepG2 cells may be useful to study regulation of drug-metabolizing enzymes.
Human hepatocytes in primary culture: the choice to investigate drug metabolism in man.
TLDR
It is considered that human hepatocytes reflect the heterogeneity of CYP expression in human liver and is a suitable model for drug metabolism studies and several key issues need to be addressed at the early stages of drug development.
Influence of culture time on the expression of drug‐metabolizing enzymes in primary human hepatocytes and hepatoma cell line HepG2
TLDR
Neither primary hepatocytes nor HepG2 cell line display a model for constant expression of drug‐metabolizing enzymes, according to real‐time RT‐PCR analysis.
Generation of human hepatocytes by stem cell technology: definition of the hepatocyte
TLDR
The present article reviews studies describing the fate of extrahepatic human stem and precursor cells in livers of laboratory animals, including the possibility of cell fusion and critically discusses the phenotype of stem cells after application of various differentiation protocols aimed at generating human hepatocytes.
Differentiation of in vitro-modified human peripheral blood monocytes into hepatocyte-like and pancreatic islet-like cells.
TLDR
The ability to reprogram, expand, and differentiate peripheral blood monocytes in large quantities opens the real possibility of the clinical application of programmable cells of monocytic origin in tissue repair and organ regeneration.
...
...