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Terasaki Institute for Biomedical Innovation

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Small, First published 9 March 2021 | https://doi.org/10.1002/smll.202007425 Bioengineered Multicellular Liver Microtissues for Modeling Advanced Hepatic Fibrosis Driven Through Non‐Alcoholic Fatty Liver Disease

Hyun-Jong Cho, Han-Jun Kim, KangJu Lee, Soufian Lasli, Aly Ung, Tyler Hoffman, Rohollah Nasiri, Praveen Bandaru, Samad Ahadian, Mehmet R. Dokmeci, Junmin Lee,^* and Ali Khademhosseini^*

Prof. H-J. Cho, Prof. H-J. Kim, S. Lasli, A. Ung, T. Hoffman,
R. Nasiri, P. Bandaru, Prof. S. Ahadian, Dr. J. Lee,
Prof. A. Khademhosseini
Department of Bioengineering
Henry Samueli School of Engineering and Applied Sciences
University of California-Los Angeles
Los Angeles, CA 90095, USA

Prof. H-J. Cho, Prof. H-J. Kim, S. Lasli, A. Ung, T. Hoffman,
R. Nasiri, P. Bandaru, Prof. S. Ahadian, Prof. M. R. Dokmeci, Dr. J. Lee,
Prof. A. Khademhosseini
Center for Minimally Invasive Therapeutics (C-MIT)
University of California-Los Angeles
Los Angeles, CA 90095, USA

Prof. H-J. Cho
College of Pharmacy
Kangwon National University
Chuncheon, Gangwon 24341, Republic of Korea

Prof. H-J. Kim, R. Nasiri, P. Bandaru, Prof. S. Ahadian,
Prof. M. R. Dokmeci, Dr. J. Lee, Prof. A. Khademhosseini
Terasaki Institute for Biomedical Innovation
Los Angeles, CA 90064, USA

Prof. K. Lee
Department of Healthcare Medical Engineering
Chonnam National University
Yeosu 59626, Republic of Korea

Prof. M. R. Dokmeci, Prof. A. Khademhosseini
Department of Radiological Sciences
David Geffen School of Medicine
University of California-Los Angeles
Los Angeles, CA 90095, USA

Prof. A. Khademhosseini
Department of Chemical and Biomolecular Engineering
Henry Samueli School of Engineering and Applied Sciences
University of California-Los Angeles
Los Angeles, CA 90095, USA

Prof. A. Khademhosseini
Jonsson Comprehensive Cancer Centre
University of California
Los Angeles, CA 90095, USA

H.‐J.C. and H.‐J.K. contributed equally to this work.

^*Corresponding author

Abstract

Despite considerable efforts in modeling liver disease in vitro, it remains difficult to recapitulate the pathogenesis of the advanced phases of non‐alcoholic fatty liver disease (NAFLD) with inflammation and fibrosis. Here, a liver‐on‐a‐chip platform with bioengineered multicellular liver microtissues is developed, composed of four major types of liver cells (hepatocytes, endothelial cells, Kupffer cells, and stellate cells) to implement a human hepatic fibrosis model driven by NAFLD: i) lipid accumulation in hepatocytes (steatosis), ii) neovascularization by endothelial cells, iii) inflammation by activated Kupffer cells (steatohepatitis), and iv) extracellular matrix deposition by activated stellate cells (fibrosis). In this model, the presence of stellate cells in the liver‐on‐a‐chip model with fat supplementation showed elevated inflammatory responses and fibrosis marker up‐regulation. Compared to transforming growth factor‐beta‐induced hepatic fibrosis models, this model includes the native pathological and chronological steps of NAFLD which shows i) higher fibrotic phenotypes, ii) increased expression of fibrosis markers, and iii) efficient drug transport and metabolism. Taken together, the proposed platform will enable a better understanding of the mechanisms underlying fibrosis progression in NAFLD as well as the identification of new drugs for the different stages of NAFLD.

논문정보

형식Research article
게재일2021년 03월 (BRIC 등록일 2021-03-18)
연구진국내+국외 연구진
분야 바이오·의료융합 > 바이오소재

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