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Cited by 172Pharmacogenetics and Drug MetabolismDrug-Induced Hepatotoxicity and ProtectionMetabolomics and Mass Spectrometry Studies

Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long-term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics

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Vorrink, Sabine U., Ullah, Shahid, Schmidt, Staffan, Nandania, Jatin, Velagapudi, Vidya, Beck, Olof, Ingelman‐Sundberg, Magnus, Lauschke, Volker M.·2017·The FASEB Journal
DOI 10.1096/fj.201601375rPMC PMC5434660
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Abstract

Adverse reactions or lack of response to medications are important concerns for drug development programs. However, faithful predictions of drug metabolism and toxicity are difficult because animal models show only limited translatability to humans. Furthermore, current in vitro systems, such as hepatic cell lines or primary human hepatocyte (PHH) 2‐dimensional (2D) monolayer cultures, can be used only for acute toxicity tests because of their immature phenotypes and inherent instability. Therefore, the migration to novel phenotypically stable models is of prime importance for the pharmaceutical industry. Novel 3‐dimensional (3D) culture systems have been shown to accurately mimic in vivo hepatic phenotypes on transcriptomic and proteomic level, but information about their metabolic stability is lacking. Using a combination of targeted and untargeted high‐resolution mass spectrometry, we found that PHHs in 3D spheroid cultures remained metabolically stable for multiple weeks, whereas metabolic patterns of PHHs from the same donors cultured as conventional 2D monolayers rapidly deteriorated. Furthermore, pharmacokinetic differences between donors were maintained in 3D spheroid cultures, enabling studies of interindividual variability in drug metabolism and toxicity. We conclude that the 3D spheroid system is metabolically stable and constitutes a suitable model for in vitro studies of long‐term drug metabolism and pharmacokinetics.—Vorrink, S. U., Ullah, S., Schmid, S., Nandania, J., Velagapudi, V., Beck, O., Ingelman‐Sundberg, M., Lauschke, V. M. Endogenous and xenobiotic metabolic stability of primary human hepatocytes in long‐term 3D spheroid cultures revealed by a combination of targeted and untargeted metabolomics. FASEB J. 31, 2696–2708 (2017). www.fasebj.org

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  • Conventional 2D cell culture systems are insufficient for sustained preservation of primary hepatocyte differentiation, polarity, and metabolic function.

    “Conventional 2D cell culture systems have been acknowledged as insufficient for the sustained preservation of PHs differentiation, polarity, and metabolic function [24,25].”

    From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [24]

    The Abstract says primary human hepatocytes rapidly dedifferentiate in conventional 2D monolayers, and the Results report loss of hepatic metabolic function in 2D culture over time. The copy describes bile canaliculi in 3D spheroids, but does not establish that 2D cultures fail to preserve hepatocyte polarity; that part of the claim is unsupported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Hepatocytes cultured in 2D systems swiftly impair liver-specific gene expression, CYP450 activity, and synthetic capability, leading to reduced viability and inadequate predictive accuracy for drug testing.

    “Across multiple studies, hepatocytes cultured in 2D systems swiftly impair liver-specific gene expression, CYP450 activity, and synthetic capability, ultimately leading to reduced viability and inadequate predictive accuracy for drug testing [24,25].”

    From The Hepatocyte Expansion Paradox: A Review of In Vitro Challenges and Advances (2026) · cites this paper as [24]

    The Results report rapid loss of liver-specific gene expression and hepatic functions in 2D culture, while the Discussion reports lower CYP activity than in 3D culture. The Abstract says 2D dedifferentiation impairs prediction of human drug metabolism. The cited paper does not establish the claimed reduction in cell viability or show that the listed changes cause it. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • The metabolite formation rates for 1-OH-midazolam and N-desethylamodiaquine observed in this study are at comparable levels to those previously observed in 3D spheroids.

    “The metabolite formation rates for 1 -OH-midazolam and N -desethylamodiaquine observed in this study are at comparable levels to those previously observed in 3D spheroids [23] .”

    From 3D microperfusion of mesoscale human microphysiological liver models improves functionality and recapitulates hepatic zonation (2023) · cites this paper as [23]

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References 69 · Cited by 172

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  1. [2]Sgro C., Clinard F., Ouazir K., Chanay H., Allard C., Guilleminet C., Lenoir C., Lemoine A., Hillon P. (2002) Incidence of drug-induced hepatic injuries: a French population-based study. Hepatology 36, 451– 455 12143055
  2. [3]Björnsson E., Olsson R. (2005) Outcome and prognostic markers in severe drug-induced liver disease. Hepatology 42, 481– 489 16025496
  3. [4]Marudanayagam R., Shanmugam V., Gunson B., Mirza D. F., Mayer D., Buckels J., Bramhall S. R. (2009) Aetiology and outcome of acute liver failure. HPB (Oxford) 11, 429– 434 19768148 PMC2742613
  4. [10]Martignoni M., Groothuis G. M. M., de Kanter R. (2006) Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opinion on Drug Metabolism &amp. Toxicology 2, 875– 894 17125407
  5. [12]Rowe C., Gerrard D. T., Jenkins R., Berry A., Durkin K., Sundstrom L., Goldring C. E., Park B. K., Kitteringham N. R., Hanley K. P., Hanley N. A. (2013) Proteome-wide analyses of human hepatocytes during differentiation and dedifferentiation. Hepatology 58, 799– 809 23526496 PMC3842115
  6. [13]Azimifar S. B., Nagaraj N., Cox J., Mann M. (2014) Cell-type-resolved quantitative proteomics of murine liver. Cell Metab. 20, 1076– 1087 25470552
  7. [14]Lauschke V. M., Vorrink S. U., Moro S. M. L., Rezayee F., Nordling Å., Hendriks D. F. G., Bell C. C., Sison-Young R., Park B. K., Goldring C. E., Ellis E., Johansson I., Mkrtchian S., Andersson T. B., Ingelman-Sundberg M. (2016) Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation. Hepatology 64, 1743– 1756 27532775
  8. [15]Sison-Young R. L., Lauschke V. M., Johann E., Alexandre E., Anthérieu S., Aerts H., Gerets H. H. J., Labbe G., Hoët D., Dorau M., Schofield C. A., Lovatt C. A., Holder J. C., Stahl S. H., Richert L., Kitteringham N. R., Jones R. P., Elmasry M., Weaver R. J., Hewitt P. G., Ingelman-Sundberg M., Goldring C. E., Park B. K. (2017) A multicenter assessment of single-cell models aligned to standard measures of cell health for prediction of acute hepatotoxicity. Arch. Toxicol. 91, 1385– 1400 27344343 PMC5316403
  9. [16]Hay M., Thomas D. W., Craighead J. L., Economides C., Rosenthal J. (2014) Clinical development success rates for investigational drugs. Nat. Biotechnol. 32, 40– 51 24406927
  10. [18]Lauschke V. M., Hendriks D. F. G., Bell C. C., Andersson T. B., Ingelman-Sundberg M. (2016) Novel 3D culture systems for studies of human liver function and assessments of the hepatotoxicity of drugs and drug candidates. Chem. Res. Toxicol. 29, 1936– 1955 27661221
  11. [19]Tostões R. M., Leite S. B., Serra M., Jensen J., Björquist P., Carrondo M. J. T., Brito C., Alves P. M. (2012) Human liver cell spheroids in extended perfusion bioreactor culture for repeated-dose drug testing. Hepatology 55, 1227– 1236 22031499
  12. [20]Bell C. C., Hendriks D. F. G., Moro S. M. L., Ellis E., Walsh J., Renblom A., Fredriksson Puigvert L., Dankers A. C. A., Jacobs F., Snoeys J., Sison-Young R. L., Jenkins R. E., Nordling Å., Mkrtchian S., Park B. K., Kitteringham N. R., Goldring C. E. P., Lauschke V. M., Ingelman-Sundberg M. (2016) Characterization of primary human hepatocyte spheroids as a model system for drug-induced liver injury, liver function and disease. Sci. Rep. 6, 25187 27143246 PMC4855186
  13. [21]Bell C. C., Lauschke V. M., Vorrink S. U., Palmgren H., Duffin R., Andersson T. B., Ingelman-Sundberg M. (2017) Transcriptional, functional and mechanistic comparisons of stem cell-derived hepatocytes, HepaRG cells and 3D human hepatocyte spheroids as predictive in vitro systems for drug-induced liver injury. [E-pub ahead of print]. Drug Metab. Dispos. PMC5363699 28137721
  14. [23]Manning F. J., Swartz M. (1995) Review of the Fialuridine (FIAU) Clinical Trials, National Academies Press, Washington, DC 25121268
  15. [24]Bowsher R. R., Compton J. A., Kirkwood J. A., Place G. D., Jones C. D., Mabry T. E., Hyslop D. L., Hatcher B. L., DeSante K. A. (1994) Sensitive and specific radioimmunoassay for fialuridine: initial assessment of pharmacokinetics after single oral doses to healthy volunteers. Antimicrob. Agents Chemother. 38, 2134– 2142 7811032 PMC284697
  16. [25]Spaggiari D., Geiser L., Daali Y., Rudaz S. (2014) A cocktail approach for assessing the in vitro activity of human cytochrome P450s: an overview of current methodologies. J. Pharm. Biomed. Anal. 101, 221– 237 24746851
  17. [26]Zhou J., Yin Y. (2016) Strategies for large-scale targeted metabolomics quantification by liquid chromatography-mass spectrometry. Analyst (Lond.) 141, 6362– 6373 27722450
  18. [27]Henry H., Sobhi H. R., Scheibner O., Bromirski M., Nimkar S. B., Rochat B. (2012) Comparison between a high-resolution single-stage Orbitrap and a triple quadrupole mass spectrometer for quantitative analyses of drugs. Rapid Commun. Mass Spectrom. 26, 499– 509 22302489
  19. [28]Eliuk S., Makarov A. (2015) Evolution of Orbitrap Mass Spectrometry Instrumentation. Annu. Rev. Anal. Chem. (Palo Alto, Calif.) 8, 61– 80 26161972
  20. [30]Tiziani S., Lodi A., Khanim F. L., Viant M. R., Bunce C. M., Günther U. L. (2009) Metabolomic profiling of drug responses in acute myeloid leukaemia cell lines. PLoS One 4, e4251 19158949 PMC2621336
  21. [31]Wang Y., Gao D., Chen Z., Li S., Gao C., Cao D., Liu F., Liu H., Jiang Y. (2013) Acridone derivative 8a induces oxidative stress-mediated apoptosis in CCRF-CEM leukemia cells: application of metabolomics in mechanistic studies of antitumor agents. PLoS One 8, e63572– e63579 23667640 PMC3646819
  22. [32]Krauss R. M., Zhu H., Kaddurah-Daouk R. (2013) Pharmacometabolomics of statin response. Clin. Pharmacol. Ther. 94, 562– 565 23945822 PMC4055080
  23. [33]Roman-Garcia P., Quiros-Gonzalez I., Mottram L., Lieben L., Sharan K., Wangwiwatsin A., Tubio J., Lewis K., Wilkinson D., Santhanam B., Sarper N., Clare S., Vassiliou G. S., Velagapudi V. R., Dougan G., Yadav V. K. (2014) Vitamin B12-dependent taurine synthesis regulates growth and bone mass. J. Clin. Invest. 124, 2988– 3002 24911144 PMC4071367
  24. [34]Vrzal R., Stejskalova L., Monostory K., Maurel P., Bachleda P., Pavek P., Dvorak Z. (2009) Dexamethasone controls aryl hydrocarbon receptor (AhR)-mediated CYP1A1 and CYP1A2 expression and activity in primary cultures of human hepatocytes. Chem. Biol. Interact. 179, 288– 296 19022236
  25. [35]Yoshinari K., Yoda N., Toriyabe T., Yamazoe Y. (2010) Constitutive androstane receptor transcriptionally activates human CYP1A1 and CYP1A2 genes through a common regulatory element in the 5′-flanking region. Biochem. Pharmacol. 79, 261– 269 19682433
  26. [36]Shan J., Schwartz R. E., Ross N. T., Logan D. J., Thomas D., Duncan S. A., North T. E., Goessling W., Carpenter A. E., Bhatia S. N. (2013) Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat. Chem. Biol. 9, 514– 520 23728495 PMC3720805
  27. [37]Oshiro C., Mangravite L., Klein T., Altman R. (2010) PharmGKB very important pharmacogene: SLCO1B1. Pharmacogenet. Genomics 20, 211– 216 19952871 PMC3086841
  28. [38]Maglich J. M., Parks D. J., Moore L. B., Collins J. L., Goodwin B., Billin A. N., Stoltz C. A., Kliewer S. A., Lambert M. H., Willson T. M., Moore J. T. (2003) Identification of a novel human constitutive androstane receptor (CAR) agonist and its use in the identification of CAR target genes. J. Biol. Chem. 278, 17277– 17283 12611900
  29. [39]Ihunnah C. A., Jiang M., Xie W. (2011) Nuclear receptor PXR, transcriptional circuits and metabolic relevance. BBA - Molecular Basis of Disease 1812, 956– 963 21295138 PMC3111845
  30. [40]Jones D. R., Gorski J. C., Haehner B. D., O’Mara E. M. Jr., Hall S. D. (1996) Determination of cytochrome P450 3A4/5 activity in vivo with dextromethorphan N‐demethylation. Clin. Pharmacol. Ther 60, 374– 384 8873685
  31. [41]Houtkooper R. H., Cantó C., Wanders R. J., Auwerx J. (2010) The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr. Rev. 31, 194– 223 20007326 PMC2852209
  32. [42]Inoue Y., Yu A.-M., Yim S. H., Ma X., Krausz K. W., Inoue J., Xiang C. C., Brownstein M. J., Eggertsen G., Björkhem I., Gonzalez F. J. (2006) Regulation of bile acid biosynthesis by hepatocyte nuclear factor 4alpha. J. Lipid Res. 47, 215– 227 16264197 PMC1413576
  33. [43]Kir S., Zhang Y., Gerard R. D., Kliewer S. A., Mangelsdorf D. J. (2012) Nuclear receptors HNF4α and LRH-1 cooperate in regulating Cyp7a1 in vivo. J. Biol. Chem. 287, 41334– 41341 23038264 PMC3510831
  34. [44]Hayes K. C., Sturman J. A. (1981) Taurine in metabolism. Annu. Rev. Nutr. 1, 401– 425 6764722
  35. [45]Chapman K. L., Holzgrefe H., Black L. E., Brown M., Chellman G., Copeman C., Couch J., Creton S., Gehen S., Hoberman A., Kinter L. B., Madden S., Mattis C., Stemple H. A., Wilson S. (2013) Pharmaceutical toxicology: designing studies to reduce animal use, while maximizing human translation. Regul. Toxicol. Pharmacol. 66, 88– 103 23524271
  36. [46]Ferguson S. S., Chen Y., LeCluyse E. L., Negishi M., Goldstein J. A. (2005) Human CYP2C8 is transcriptionally regulated by the nuclear receptors constitutive androstane receptor, pregnane X receptor, glucocorticoid receptor, and hepatic nuclear factor 4alpha. Mol. Pharmacol. 68, 747– 757 15933212
  37. [47]Sahi J., Shord S. S., Lindley C., Ferguson S., LeCluyse E. L. (2009) Regulation of cytochrome P450 2C9 expression in primary cultures of human hepatocytes. J. Biochem. Mol. Toxicol. 23, 43– 58 19202563
  38. [48]Goodwin B., Hodgson E., Liddle C. (1999) The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol. Pharmacol. 56, 1329– 1339 10570062
  39. [49]Sugatani J., Nishitani S., Yamakawa K., Yoshinari K., Sueyoshi T., Negishi M., Miwa M. (2005) Transcriptional regulation of human UGT1A1 gene expression: activated glucocorticoid receptor enhances constitutive androstane receptor/pregnane X receptor-mediated UDP-glucuronosyltransferase 1A1 regulation with glucocorticoid receptor-interacting protein 1. Mol. Pharmacol. 67, 845– 855 15557560
  40. [50]Renwick A. B., Watts P. S., Edwards R. J., Barton P. T., Guyonnet I., Price R. J., Tredger J. M., Pelkonen O., Boobis A. R., Lake B. G. (2000) Differential maintenance of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab. Dispos. 28, 1202– 1209 10997941
  41. [52]Venkatakrishnan K., Obach R. S. (2005) In vitro-in vivo extrapolation of CYP2D6 inactivation by paroxetine: prediction of nonstationary pharmacokinetics and drug interaction magnitude. Drug Metab. Dispos. 33, 845– 852 15788540
  42. [53]Schmid B., Bircher J., Preisig R., Küpfer A. (1985) Polymorphic dextromethorphan metabolism: co-segregation of oxidative O-demethylation with debrisoquin hydroxylation. Clin. Pharmacol. Ther. 38, 618– 624 4064464
  43. [54]Lauschke V. M., Ingelman-Sundberg M. (2016) The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity. Int. J. Mol. Sci. 17, E 1714 PMC5085745 27754327
  44. [55]Ranninger C., Schmidt L. E., Rurik M., Limonciel A., Jennings P., Kohlbacher O., Huber C. G. (2016) Improving global feature detectabilities through scan range splitting for untargeted metabolomics by high-performance liquid chromatography–Orbitrap mass spectrometry. Anal. Chim. Acta 930, 13– 22 27265900
  45. [56]Najdekr L., Friedecký D., Tautenhahn R., Pluskal T., Wang J., Huang Y., Adam T. (2016) Influence of mass resolving power in orbital ion-trap mass spectrometry-based metabolomics. Anal. Chem. 88, 11429– 11435 27809493
  46. [57]Cajka T., Fiehn O. (2016) Toward Merging Untargeted and Targeted Methods in Mass Spectrometry-Based Metabolomics and Lipidomics. Anal. Chem. 88, 524– 545 26637011
  47. [58]Roe B., Kensicki E., Mohney R., Hall W. W. (2011) Metabolomic profile of hepatitis C virus-infected hepatocytes. PLoS One 6, e23641 21853158 PMC3154941
  48. [59]Meissen J. K., Hirahatake K. M., Adams S. H., Fiehn O. (2015) Temporal metabolomic responses of cultured HepG2 liver cells to high fructose and high glucose exposures. Metabolomics 11, 707– 721 26190955 PMC4504739
  49. [60]García-Cañaveras J. C., Castell J. V., Donato M. T., Lahoz A. (2016) A metabolomics cell-based approach for anticipating and investigating drug-induced liver injury. Sci. Rep. 6, 27239 27265840 PMC4893700
  50. [61]Brown M. V., Compton S. A., Milburn M. V., Lawton K. A., Cheatham B. (2013) Metabolomic signatures in lipid-loaded HepaRGs reveal pathways involved in steatotic progression. Obesity (Silver Spring) 21, E561– E570 23512965 PMC3689848
  51. [62]Van den Eede N., Cuykx M., Rodrigues R. M., Laukens K., Neels H., Covaci A., Vanhaecke T. (2015) Metabolomics analysis of the toxicity pathways of triphenyl phosphate in HepaRG cells and comparison to oxidative stress mechanisms caused by acetaminophen. Toxicol. In Vitro 29, 2045– 2054 26318275
  52. [63]Jeon S.-M. (2016) Regulation and function of AMPK in physiology and diseases. Exp. Mol. Med. 48, e245 27416781 PMC4973318
  53. [64]Häberle J., Boddaert N., Burlina A., Chakrapani A., Dixon M., Huemer M., Karall D., Martinelli D., Crespo P. S., Santer R., Servais A., Valayannopoulos V., Lindner M., Rubio V., Dionisi-Vici C. (2012) Suggested guidelines for the diagnosis and management of urea cycle disorders. Orphanet J. Rare Dis. 7, 32 22642880 PMC3488504
  54. [65]Kim S.-R., Kubo T., Kuroda Y., Hojyo M., Matsuo T., Miyajima A., Usami M., Sekino Y., Matsushita T., Ishida S. (2014) Comparative metabolome analysis of cultured fetal and adult hepatocytes in humans. J. Toxicol. Sci. 39, 717– 723 25242401
  55. [66]Gripon P., Rumin S., Urban S., Le Seyec J., Glaise D., Cannie I., Guyomard C., Lucas J., Trepo C., Guguen-Guillouzo C. (2002) Infection of a human hepatoma cell line by hepatitis B virus. Proc. Natl. Acad. Sci. USA 99, 15655– 15660 12432097 PMC137772
  56. [67]Kanebratt K. P., Andersson T. B. (2008) Evaluation of HepaRG cells as an in vitro model for human drug metabolism studies. Drug Metab. Dispos. 36, 1444– 1452 18385292
  57. [68]Anthérieu S., Chesné C., Li R., Camus S., Lahoz A., Picazo L., Turpeinen M., Tolonen A., Uusitalo J., Guguen-Guillouzo C., Guillouzo A. (2010) Stable expression, activity, and inducibility of cytochromes P450 in differentiated HepaRG cells. Drug Metab. Dispos. 38, 516– 525 20019244
  58. [69]Baxter M., Withey S., Harrison S., Segeritz C.-P., Zhang F., Atkinson-Dell R., Rowe C., Gerrard D. T., Sison-Young R., Jenkins R., Henry J., Berry A. A., Mohamet L., Best M., Fenwick S. W., Malik H., Kitteringham N. R., Goldring C. E., Piper Hanley K., Vallier L., Hanley N. A. (2015) Phenotypic and functional analyses show stem cell-derived hepatocyte-like cells better mimic fetal rather than adult hepatocytes. J. Hepatol. 62, 581– 589 25457200 PMC4334496
  59. [70]Yu A., Haining R. L. (2001) Comparative contribution to dextromethorphan metabolism by cytochrome P450 isoforms in vitro: can dextromethorphan be used as a dual probe for both CTP2D6 and CYP3A activities? Drug Metab. Dispos. 29, 1514– 1520 11602530

Authors
Vorrink, S. U., Ullah, S., Schmidt, S., Nandania, J., Velagapudi, V., Beck, O., Ingelman‐Sundberg, M., & Lauschke, V. M.
Affiliations
  • Section of Pharmacogenetics Department of Physiology and Pharmacology
  • Karolinska Institutet (SE)
  • University of Helsinki (FI)
Corresponding author
Lauschke, Volker M.
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2017-03-06
Volume
31
Issue
6
Pages
2696-2708
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.201601375r
PMC
PMC5434660
OpenAlex
W2592130743
Cited by
172
References
69
Citations by year
2026: 15 · 2025: 19 · 2024: 16 · 2023: 22 · 2022: 9 · 2021: 29 · 2020: 23 · 2019: 15 · 2018: 17 · 2017: 6
FWCI
17.74
Type
journal article
Language
en
Open access
Licence
Locations
  • The FASEB Journal (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Työväentutkimus Vuosikirja (submittedVersion)
Funders
  • Innovative Medicines Initiative (115336)
  • Vetenskapsrådet (2016‐01153, 2016‐01154)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Keywords
primary human hepatocytes, 3D spheroid culture, metabolic stability, xenobiotic metabolism, endogenous metabolism, interindividual variability, pharmacokinetics, in vitro toxicity models, hepatocyte monolayer culture, untargeted metabolomics, targeted metabolomics
MeSH terms
Cell Line, Gene Expression Regulation, Humans, Xenobiotics, Cell Culture Techniques, Hepatocytes, Metabolomics

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