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Enhanced hepatic functions of genetically modified mouse hepatoma cells by spheroid culture for drug toxicity screening

01:20 EDT 23 Aug 2017 | Wiley Biotechnology Journal

While hepatic cell lines are mainly used for in vitro drug induced toxicity studies, they exhibit limited functionalities. To overcome this, we have employed genetically engineered mouse hepatoma cells, Hepa/8F5, wherein expression of liver enriched transcription factors is induced by doxycycline leading to increased functionality. Further enhancement in functionality was achieved by spheroid culture in a previously developed 3D cell culture platform. Cells were seeded in presence of temperature‐responsive poly(N‐isopropylacrylamide) on poly(N‐isopropylacrylamide‐co‐gelatin) cryogel scaffold based high throughput platform. Cells seeded in presence of poly(N‐isopropylacrylamide) and induced with doxycycline exhibited highest functionalities. There was an increase of ∼26, 36 and 39% in albumin secretion, ammonia removal and CYP3A4 activity, respectively. Morphological analysis showed arrest in cell proliferation and enlarged nucleus in presence of doxycyline and spheroid formation in presence of poly(N‐isopropylacrylamide). Drug induced liver toxicity studies revealed that cells induced with doxycycline were resistive to tamoxifen but sensitive to acetaminophen whereas, cultures initiated in presence of poly(N‐isopropylacrylamide) were resistive to both the drugs which is indicative of diffusional barrier of the spheroids. We conclude that Hepa/8F5 cells show enhanced functionality in cryogel based spheroid culture platform which can be successfully used for high throughput screening of hepatic toxicity in vitro.

Original Article: Enhanced hepatic functions of genetically modified mouse hepatoma cells by spheroid culture for drug toxicity screening

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