title: A 3D alcoholic liver disease model on a chip.
abstract: Alcohol is one of the main causes of liver diseases, and the development of alcoholic liver disease (ALD) treatment methods has been one of the hottest issues. For this purpose, development of in vitro models mimicking the in vivo physiology is one of the critical requirements, and they help to determine the disease mechanisms and to discover the treatment method. Herein, a three-dimensional (3D) ALD model was developed and its superior features in mimicking the in vivo condition were demonstrated. A spheroid-based microfluidic chip was employed for the development of the 3D in vitro model of ALD progression. We co-cultured rat primary hepatocytes and hepatic stellate cells (HSCs) in a fluidic chip to investigate the role of HSCs in the recovery of liver with ALD. An interstitial level of flow derived by an osmotic pump was applied to the chip to provide in vivo mimicking of fluid activity. Using this in vitro tool, we were able to observe structural changes and decreased hepatic functions with the increase in ethanol concentration. The recovery process of liver injured by alcohol was observed by providing fresh culture medium to the damaged 3D liver tissue for few days. A reversibly- and irreversibly-injured ALD model was established. The proposed model can not only be used for the research of alcoholic disease mechanism, but also has the potential for use in studies of hepatotoxicity and drug screening applications.
authors: KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 136-713, Republic of Korea.
authors: JaeSeo
authors: J
authors: Lee
authors: School of Biomedical Engineering, College of Health Science, Korea University, Seoul 136-713, Republic of Korea.
authors: BongHwan
authors: B
authors: Choi
authors: Department of Bioengineering, School of Engineering and Medicine, Stanford University, 318 Campus Drive, Stanford, CA 94305, USA.
authors: Da Yoon
authors: da Y
authors: No
authors: KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 136-713, Republic of Korea.
authors: GeonHui
authors: G
authors: Lee
authors: Department of Biopharmaceutical Sciences College of Pharmacy University of Illinois at Chicago, USA.
authors: Seung-Ri
authors: SR
authors: Lee
authors: Department of Biomedical Engineering, College of Health Science, Korea University, Seoul 136-713, Republic of Korea. dbiomed@korea.ac.kr and MicroFIT R&BD Institute, Dunchon-daero 457beon-gil, Jungwon-gu, Gyeonggi-do 462-806, Republic of Korea.
authors: HyunJik
authors: H
authors: Oh
authors: KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 136-713, Republic of Korea and Department of Biomedical Engineering, College of Health Science, Korea University, Seoul 136-713, Republic of Korea. dbiomed@korea.ac.kr.
authors: Sang-Hoon
authors: SH
authors: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003198:Computer Simulation; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008108:Liver Diseases, Alcoholic / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008954:Models, Biological; D051381:Rats; D018874:Spheroids, Cellular
chemical_list: D000199:Actins; D053148:Caspase 3; D000431:Ethanol; C498862:Acta2 protein, rat; C505410:Casp3 protein, rat