Abstract
Hepatocytes are parenchymal cells of the liver responsible for drug detoxification, urea and bile production, serum protein synthesis, and glucose homeostasis. Hepatocytes are widely used for drug toxicity studies in bioartificial liver devices and for cell-based liver therapies. Because hepatocytes are highly differentiated cells residing in a complex microenvironment in vivo, they tend to lose hepatic phenotype and function in vitro. This paper first reviews traditional culture approaches used to rescue hepatic function in vitro and then discusses the benefits of emerging microfluidic-based culture approaches. We conclude by reviewing integration of hepatocyte cultures with bioanalytical or sensing approaches.
Highlights
The liver is the largest organ in the body and the major site of xenobiotic metabolism
The abnormal accumulation of lipids or steatosis in the liver is known as nonalcoholic fatty liver disease (NAFLD), and it can evolve into nonalcoholic steatohepatitis (NASH) characterized by chronic liver inflammation and hepatocyte cell death.[10,13,17,18,19]
The basolateral membrane of hepatocytes is equipped with different adenosine triphosphate (ATP) binding cassettes (ABC), such as bile salt export pump (BSEP), multidrug resistance protein 1 (MRP1), MRP2, MRP3, and ABCG5/G8 for excretion of bile acids, lipophilic cationic drugs, non-bile acid organic anions, phospholipids, and cholesterol
Summary
The liver is the largest organ in the body and the major site of xenobiotic metabolism. There has been a strong interest in culturing hepatocytes in order to model liver diseases or predict liver toxicity. In vitro cultures have sought to recapitulate elements of the native liver microenvironment by creating co-cultures of hepatocytes with non-hepatic cells and by incorporating extracellular matrix (ECM) components.[1,2]. In this Review, we first highlight the essential functions of the liver cells and available cell sources for in vitro studies along with traditional methods for cultivation of hepatocytes. We discuss hepatocyte cultures in microfluidic devices and integration of bioanalytical tools into such microfluidic cultures (see Fig. 1)
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