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Morphological and Biochemical Integrity of Human Liver Slices in Long-Term Culture: Effects of Oxygen Tension

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Abstract

We tested the effects of low 20% O2) and high (70% O2) oxygen tension on the morphological and biochemical integrity of human liver slices incubated for up to 72 h in supplemented Williams' E medium in a dynamic rotating culture system. High oxygen tension was more effective than low oxygen tension for preserving morphological integrity in long-term culture 48–72 h). After 72 h of culture with 70% O2, the lobular pattern was well preserved, and the survival of hepatocytes approximately 80%) and other cell types was good. Immunohistochemical studies showed good preservation of the region-specific expression of CYP2E1 and CYP3A4 isoenzymes for up to 72 h of incubation in 70% O2. As compared to 20% O2, the oxidized glutathione content and reactive oxygen species production were slightly increased in 70% O2, suggesting that minimal oxidative stress occurred with the high oxygen tension. In conclusion, despite slight oxidative stress associated with high oxygen tension, 70% O2 appeared more appropriate than 20% O2 for preserving the morphological and biochemical integrity of human liver slices cultured in a dynamic organ culture system for up to 72 h.

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Authors and Affiliations

  1. Drug Safety Evaluation, Aventis Pharma SA, Vitry-sur-Seine, France

    H. Martin, J.P. Sarsat, C. Lerche-Langrand, H. Toutain & V. Albaladejo

  2. INSERM U490, Centre Universitaire des Saints-Pères, Paris, France

    H. Martin

  3. Centre de Recherches Chirurgicales, Faculté de Médecine Saint-Antoine, INSERM U402 and, Paris, France

    C. Housset & P. Balladur

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  1. H. Martin
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  2. J.P. Sarsat
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Martin, H., Sarsat, J., Lerche-Langrand, C. et al. Morphological and Biochemical Integrity of Human Liver Slices in Long-Term Culture: Effects of Oxygen Tension. Cell Biol Toxicol 18, 73–85 (2002). https://doi.org/10.1023/A:1015379815897

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