Necroptosis Is a Mechanism of Death in Mouse Induced Hepatocyte-Like Cells Reprogrammed from Mouse Embryonic Fibroblasts
Yun-Suk Lee1, Kyung-Mee Park2, Lina Yu3, Ho-Hyun Kwak3, Hee-Jun Na1, Kyung-Sun Kang4, and
Heung-Myong Woo3,*
1Hauul Bio Incorporation, Chuncheon 24398, Korea,2College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Korea, 3College of Veterinary Medicine, Kangwon National University, Chuncheon 24341, Korea, 4Adult Stem Cell Research Center, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea
*Correspondence: woohm@kangwon.ac.kr
Received December 10, 2017; Revised May 13, 2018; Accepted June 5, 2018.; Published online July 10, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
Liver transplantation is recommended for patients with liver failure, but liver donors are limited. This necessitates the development of artificial livers, and hepatocytes are necessary to develop such artificial livers. Although induced hepatocytelike cells are used in artificial livers, the characteristics of mouse induced hepatocyte-like cells (miHeps) reprogrammed with embryonic fibroblasts have not yet been clarified. Therefore, this study investigated the mechanisms underlying the survival, function, and death of miHeps. miHeps showed decreased cell viability, increased cytotoxicity, decreased hepatic function, and albumin and urea secretion at passage 14. Addition of necrostatin-1 (NEC-1) to miHeps inhibited necrosome formation and reactive oxygen species generation and increased cell survival. However, NEC-1 did not affect the hepatic function of miHeps. These results provide a basis for development of artificial livers using hepatocytes.
Keywords: artificial liver, mouse induced hepatocyte-like cells,
necroptosis, necrostatin-1, necrosome formation


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30 June 2018 Volume 41,
Number 6, pp. 495~611

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