A microfluidic patterned model of non-alcoholic fatty liver disease: applications to disease progression and zonation. Issue 18 (29th August 2019)

• Record Type: Journal Article
• Authors: Bulutoglu, Beyza; Rey-Bedón, Camilo; Kang, Young Bok (Abraham); Mert, Safak; Yarmush, Martin L.; Usta, O. Berk
• Is Part Of: Lab on a chip. Volume 19:Issue 18(2019)
• Page Start: 3022
• Page End: 3031
• Publication Date: 2019-08-29
• Subjects: Miniature electronic equipment -- Periodicals; Combinatorial chemistry -- Periodicals; Biotechnology -- Periodicals; 543.0813
• DOI: 10.1039/c9lc00354a
• Languages: English
• ISSNs: 1473-0197

Abstract

Abstract : Non-alcoholic fatty liver disease (NAFLD) involves a progressive increase of lipid accumulation. We created a microfluidic progressive NAFLD platform using free fatty acid gradients to capture the wide spectrum of disease conditions in a single continuous liver tissue. Abstract : Non-alcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH) affect 25% of the world population. NAFLD is predicted to soon become the main cause of liver morbidity and transplantation. The disease is characterized by a progressive increase of lipid accumulation in hepatocytes, which eventually induce fibrosis and inflammation, and can ultimately cause cirrhosis and hepatic carcinoma. Here, we created a patterned model of NAFLD on a chip using free fatty acid gradients to recapitulate a spectrum of disease conditions in a single continuous liver tissue. We established the NAFLD progression via quantification of intracellular lipid accumulation and transcriptional levels of fatty acid transporters and NAFLD pathogenesis markers. We then used this platform to create oxygen driven steatosis zonation mimicking the sinusoidal lipid distribution on a single continuous tissue and showed that this fat zonation disappears under progressed steatosis, in agreement with in vivo observations and recent computational studies. While we focus on free fatty acids and oxygen as the drivers of NAFLD, the microfluidic platform here is extensible to simultaneous use of other drivers.