Dynamic Liver\nChip Based on Well-Coupled Microfluidics:\nAn Accurate NASH Model for Drug Evaluation

The convenient liver model in vitro recapitulating the\nhepatic\nfunctions, metabolism, and even steatohepatitis to perform the accurate\ndrug evaluation is still challenging because of the unattainable hominine\nphysiological microenvironment in vitro. Here, the progressed stages\nof nonalcoholic steatohepatitis (NASH) disease were precisely modeled\nto accurately evaluate the performance of antilipemic based on the\ndynamic liver chip adopting the well-coupled microfluidics, which\nwell recapitulated the normal and steatohepatitis of liver in vitro.\nIn brief, the mild nutrient flow and sufficient oxygen supply for\nparenchymal liver cells could be well supplied through the endothelial\ncells layer that mimicked the real physiological barrier of endothelium,\nwhile the loading of drugs might be obtained by directly adding drug\ninto the running nutrient flow to mimic the intravenously administrable.\nThe progressed degree of steatohepatitis could be directly reflected\nby the amount of intramyocellular lipid content (IMLC) of the HepG2\ncell hepatocyte layer in wells that were induced by different concentrations\nof free fatty acids (FFA). To prove the concept of the liver chip\nin drug evaluation, an accurate assessment of the performance of firsocostat,\nthe acetyl-CoA carboxylase (ACC) inhibitor of hepatic mitochondria\nof hepatocytes, was carried out. The subtle time dependence of firsocostat\ntreatment to different progressed stages of NASH was clearly figured\nout. Therefore, we prospect the liver chip that adopted well-coupled\nmicrofluidics could be an accurate and standard liver model in vitro\nto carry out the antilipemic evaluation and screening, which significantly\nenlightens the drug evaluation by liver on chip in vitro.