A microfluidic patterned model of non-alcoholic fatty liver disease: applications to disease progression and zonation
Year: 2019
Type: article
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.
Source: Lab on a Chip
DOI: 10.1039/c9lc00354a
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Real Time Elucidation of Drug-Drug Interactions via Dual Reporter Cell Technology and Microfabricated Arrays, High Quality Long Term Preservation of Sporozoites via Deep Supercooling, Bioactive Nanoparticles for Improved Healing in Chronic Wounds, G4098304373, Novel Microfluidic Platforms for Actively Controlled in-vitro Liver Zonation, Real Time Functional Genomics of Metabolism/Cell Arrays, G8288972990, Bio-MicroElectroMechanical Systems (BioMEMS) Resource Center, G8926709065
OpenAlex ID: W2968826911
