Issue 18, 2019

A microfluidic patterned model of non-alcoholic fatty liver disease: applications to disease progression and zonation

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.

Graphical abstract: A microfluidic patterned model of non-alcoholic fatty liver disease: applications to disease progression and zonation

Supplementary files

Article information

Article type
Paper
Submitted
12 ኤፕሪ 2019
Accepted
12 ኦገስ 2019
First published
16 ኦገስ 2019

Lab Chip, 2019,19, 3022-3031

A microfluidic patterned model of non-alcoholic fatty liver disease: applications to disease progression and zonation

B. Bulutoglu, C. Rey-Bedón, Y. B. (. Kang, S. Mert, M. L. Yarmush and O. B. Usta, Lab Chip, 2019, 19, 3022 DOI: 10.1039/C9LC00354A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements