Expression and function of CYP enzymes and hepatobiliary transporters in an improved long-term sandwich culture hepatocyte model

expression-and-function-of-cyp-enzymes-and-hepatobiliary-transporters-in-an-improved-long-term-sandwich-culture-hepatocyte-model
Expression and function of CYP enzymes and hepatobiliary transporters in an improved long-term sandwich culture hepatocyte model

References

  1. Fernandez-Checa, J. C. et al. Advanced preclinical models for evaluation of drug-induced liver injury – consensus statement by the European Drug-Induced liver injury network [PRO-EURO-DILI-NET]. J. Hepatol. 75, 935–959 (2021).

    Google Scholar 

  2. Kuna, L. et al. Models of drug induced liver injury (DILI) – Current issues and future perspectives. Curr. Drug Metab. 19, 830–838 (2018).

    Google Scholar 

  3. Susukida, T., Sekine, S., Nozaki, M., Tokizono, M. & Ito, K. Prediction of the clinical risk of Drug-Induced cholestatic liver injury using an in vitro sandwich cultured hepatocyte assay. Drug Metab. Dispos. 43, 1760–1768 (2015).

    Google Scholar 

  4. Bonn, B., Svanberg, P., Janefeldt, A., Hultman, I. & Grime, K. Determination of human hepatocyte intrinsic clearance for slowly metabolized compounds: comparison of a primary hepatocyte/Stromal cell Co-culture with plated primary hepatocytes and HepaRG. Drug Metab. Dispos. 44, 527–533 (2016).

    Google Scholar 

  5. Macko, P., Palosaari, T. & Whelan, M. Extrapolating from acute to chronic toxicity in vitro. Toxicol. Vitro. 76, 105206 (2021).

    Google Scholar 

  6. McKim, J. Jr Building a tiered approach to in vitro predictive toxicity screening: A focus on assays with in vivo relevance. Comb. Chem. High. Throughput Screen. 13, 188–206 (2010).

    Google Scholar 

  7. Wilkening, S. & Bader, A. Influence of culture time on the expression of drug-metabolizing enzymes in primary human hepatocytes and hepatoma cell line HepG2. J. Biochem. Mol. Toxicol. 17, 207–213 (2003).

    Google Scholar 

  8. Bell, C. C. et al. Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease. Sci. Rep. 6, 25187 (2016).

    Google Scholar 

  9. Hu, H. et al. Long-Term expansion of functional mouse and human hepatocytes as 3D organoids. Cell 175, 1591–1606e19 (2018).

    Google Scholar 

  10. Riede, J., Wollmann, B. M., Molden, E. & Ingelman-Sundberg, M. Primary human hepatocyte spheroids as an in vitro tool for investigating drug compounds with low hepatic clearance. Drug Metab. Dispos. 49, 501–508 (2021).

    Google Scholar 

  11. Ueyama-Toba, Y. et al. Development of a hepatic differentiation method in 2D culture from primary human hepatocyte-derived organoids for pharmaceutical research. iScience 27, 110778 (2024).

    Google Scholar 

  12. Bale, S. S. et al. Long-Term coculture strategies for primary hepatocytes and liver sinusoidal endothelial cells. Tissue Eng. Part. C Methods. 21, 413–422 (2015).

    Google Scholar 

  13. Katsuda, T. et al. Generation of human hepatic progenitor cells with regenerative and metabolic capacities from primary hepatocytes. eLife 8, e47313 (2019).

    Google Scholar 

  14. Jellali, R. et al. Long-term human primary hepatocyte cultures in a microfluidic liver biochip show maintenance of mRNA levels and higher drug metabolism compared with petri cultures. Biopharm. Drug Dispos. 37, 264–275 (2016).

    Google Scholar 

  15. Byeon, J. H., Jung, D. J., Han, H. J., Son, W. C. & Jeong, G. S. Fast formation and maturation enhancement of human liver organoids using a liver-organoid-on-a-chip. Front. Cell. Dev. Biol. 12, 1452485 (2024).

    Google Scholar 

  16. Kaur, I. et al. Primary hepatocyte isolation and cultures: technical Aspects, challenges and advancements. Bioengineering 10, 131 (2023).

    Google Scholar 

  17. Mun, S. J. et al. Long-Term expansion of functional human pluripotent stem Cell-Derived hepatic organoids. Int. J. Stem Cells. 13, 279–286 (2020).

    Google Scholar 

  18. Shinohara, M. et al. Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system. Sci. Rep. 11, 5437 (2021).

    Google Scholar 

  19. Shoemaker, J. T. et al. A 3D cell culture Organ-on-a-Chip platform with a breathable hemoglobin analogue augments and extends primary human hepatocyte functions in vitro. Front. Mol. Biosci. 7, 568777 (2020).

    Google Scholar 

  20. Hu, Y. et al. Research progress and application of liver organoids for disease modeling and regenerative therapy. J. Mol. Med. 102, 859–874 (2024).

    Google Scholar 

  21. Sugahara, G. et al. Long-term cell fate and functional maintenance of human hepatocyte through Stepwise culture configuration. FASEB J 37, (2023).

  22. Handin, N. et al. Conditions for maintenance of hepatocyte differentiation and function in 3D cultures. iScience 24, 103235 (2021).

    Google Scholar 

  23. Horiuchi, S. et al. Formation of functional, extended bile canaliculi, and increased bile acid production in sandwich-cultured human cryopreserved hepatocytes using commercially available culture medium. Arch. Toxicol. 98, 2605–2617 (2024).

    Google Scholar 

  24. Liu, Y. et al. Generation and characterization of mature hepatocyte organoids for liver metabolic studies. J. Cell. Sci. 137, jcs261961 (2024).

    Google Scholar 

  25. Meneses-Lorente, G. et al. Utility of Long-Term cultured human hepatocytes as an in vitro model for cytochrome P450 induction. Drug Metab. Dispos. 35, 215–220 (2007).

    Google Scholar 

  26. Tong, Y. et al. Efficient hepatocyte differentiation of primary human hepatocyte-derived organoids using three dimensional nanofibers (HYDROX) and their possible application in hepatotoxicity research. Sci. Rep. Nat. Publ Group. 14, 10846 (2024).

    Google Scholar 

  27. Chen, Y. et al. Assessment of long-term functional maintenance of primary human hepatocytes to predict drug-induced hepatoxicity in vitro. Arch. Toxicol. 95, 2431–2442 (2021).

    Google Scholar 

  28. Katsuda, T. et al. Long-term maintenance of functional primary human hepatocytes using small molecules. FEBS Lett. 594, 114–125 (2019).

    Google Scholar 

  29. Xiang, C. et al. Long-term functional maintenance of primary human hepatocytes in vitro. Science 364, 399–402 (2019).

    Google Scholar 

  30. Cicchini, C. et al. Molecular mechanisms controlling the phenotype and the EMT / MET dynamics of hepatocyte. Liver Int. 35, 302–310 (2015).

    Google Scholar 

  31. LeCluyse, E. L. Human hepatocyte culture systems for the in vitro evaluation of cytochrome P450 expression and regulation. Eur. J. Pharm. Sci. 13, 343–368 (2001).

    Google Scholar 

  32. Zhong, Y., Yu, J. S., Wang, X., Binas, B. & Yoo, H. H. Chemical-based primary human hepatocyte monolayer culture for the study of drug metabolism and hepatotoxicity: comparison with the spheroid model. FASEB J 35, (2021).

  33. Bell, C. C. et al. Comparison of hepatic 2D sandwich cultures and 3D spheroids for Long-term toxicity applications: A multicenter study. Toxicol. Sci. 162, 655–666 (2018).

    Google Scholar 

  34. Jigorel, E., Le Vee, M., Boursier-Neyret, C., Parmentier, Y. & Fardel, O. Differential regulation of sinusoidal and canalicular hepatic drug transporter expression by xenobiotics activating drug-Sensing receptors in primary human hepatocytes. Drug Metab. Dispos. 34, 1756–1763 (2006).

    Google Scholar 

  35. Luttringer, O. et al. Influence of isolation procedure, extracellular matrix and dexamethasone on the regulation of membrane transporters gene expression in rat hepatocytes. Biochem Pharmacol. 1637–1650 (2002).

  36. Mickols, E. et al. OCT1 (SLC22A1) transporter kinetics and regulation in primary human hepatocyte 3D spheroids. Sci. Rep. Nat. Publ Group. 14, 17334 (2024).

    Google Scholar 

  37. Ebner, T., Ishiguro, N. & Taub, M. E. The use of transporter probe drug cocktails for the assessment of transporter-Based drug–Drug interactions in a clinical Setting—Proposal of a four component transporter cocktail. J. Pharm. Sci. 104, 3220–3228 (2015).

    Google Scholar 

  38. Guo, C., Brouwer, K. L. R., Brouwer, K. R., Stewart, P. W. & Mosley, C. Probe cocktail to assess transporter function in Sandwich-Cultured human hepatocytes. J. Pharm. Pharm. Sci. 22, 567–575 (2019).

    Google Scholar 

  39. Järvinen, E., Hammer, H. S., Pötz, O., Ingelman-Sundberg, M. & Stage, T. B. 3D spheroid primary human hepatocytes for prediction of cytochrome P450 and drug transporter induction. Clin. Pharmacol. Ther. 113, 1284–1294 (2023).

    Google Scholar 

  40. Wegler, C. et al. Global variability analysis of mRNA and protein concentrations across and within human tissues. NAR Genomics Bioinforma. 2, lqz010 (2020).

    Google Scholar 

Download references