Microscale 3D Liver Bioreactor for In Vitro Hepatotoxicity Testing under Perfusion Conditions [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 621.3 Electrical, magnetic, optical, communications, computer engineering; electronics, lighting

Thông tin xuất bản: Los Alamos, N.M. : Oak Ridge, Tenn. : Los Alamos National Laboratory ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2018

Mô tả vật lý: Size: Article No. 24 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 260245

 The accurate prediction of hepatotoxicity demands validated human in vitro models that can close the gap between preclinical animal studies and clinical trials. In this study we investigated the response of primary human liver cells to toxic drug exposure in a perfused microscale 3D liver bioreactor. The cellularized bioreactors were treated with 5, 10, or 30 mM acetaminophen (APAP) used as a reference substance. Lactate production significantly decreased upon treatment with 30 mM APAP (p <
  0.05) and ammonia release significantly increased in bioreactors treated with 10 or 30 mM APAP (p <
  0.0001), indicating APAP-induced dose-dependent toxicity. The release of prostaglandin E2 showed a significant increase at 30 mM APAP (p <
  0.05), suggesting an inflammatory reaction towards enhanced cellular stress. The expression of genes involved in drug metabolism, antioxidant reactions, urea synthesis, and apoptosis was differentially influenced by APAP exposure. Histological examinations revealed that primary human liver cells in untreated control bioreactors were reorganized in tissue-like cell aggregates. These aggregates were partly disintegrated upon APAP treatment, lacking expression of hepatocyte-specific proteins and transporters. In conclusion, our results validate the suitability of the microscale 3D liver bioreactor to detect hepatotoxic effects of drugs in vitro under perfusion conditions.
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