An in vitro model of hepatic steatosis using lipid loaded induced pluripotent stem cell derived hepatocyte like cells

Authors

  • Hiraganahalli Bhaskar Deepak Jubilant Biosys Limited
  • Nellikalaya Shreekrishna Jubilant Biosys Limited
  • Zaheerbasha Sameermahmood Jubilant Biosys Limited
  • Niranjan Naranapur Anand Jubilant Biosys Limited
  • Raghotham Hulgi Jubilant Biosys Limited
  • Juluri Suresh Jubilant Biosys Limited
  • Sonal Khare Jubilant Biosys Limited
  • Saravanakumar Dhakshinamoorthy Jubilant Biosys Limited

DOI:

https://doi.org/10.14440/jbm.2020.330

Keywords:

iPSC, hepatocyte-like cells, hepatic steatosis

Abstract

Hepatic steatosis is a metabolic disease, characterized by selective and progressive accumulation of lipids in liver, leading to progressive non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and cirrhosis. The existing in vitro models of hepatic steatosis to elucidate the molecular mechanisms behind the onset of hepatic steatosis and to profile small molecule modulators uses lipid loaded primary hepatocytes, and cell lines like HepG2. The limitation of these models includes high variability between the different donor samples, reproducibility, and translatability to physiological context. An in vitro human hepatocyte derived model that mimics the pathophysiological changes seen in hepatic steatosis may provide an alternative tool for pre-clinical drug discovery research. We report the development of an in vitro experimental model of hepatic steatosis using human induced pluripotent stem cell (iPSC) derived hepatocytes like cells (HLC), loaded with lipids. Our data suggests that HLC carry some of the functional characteristics of primary hepatocytes and are amenable for development of an in vitro steatosis model using lipid loading method. The in vitro experimental model of hepatic steatosis was further characterized using biomarker analysis and validated using telmisartan. With some refinement and additional validation, our in vitro steatosis model system may be useful for profiling small molecule inhibitors and studying the mechanism of action of new drugs.

Author Biography

Saravanakumar Dhakshinamoorthy, Jubilant Biosys Limited

Vice President and Head

Discovery Biology

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Published

2020-07-22

How to Cite

1.
Deepak HB, Shreekrishna N, Sameermahmood Z, Anand NN, Hulgi R, Suresh J, Khare S, Dhakshinamoorthy S. An in vitro model of hepatic steatosis using lipid loaded induced pluripotent stem cell derived hepatocyte like cells. J Biol Methods [Internet]. 2020Jul.22 [cited 2021Aug.2];7(3):e135. Available from: https://jbmethods.org/jbm/article/view/330

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