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| Efficient generation of functional hepatocyte-like cells from mouse liver progenitor cells via indirect co-culture with immortalized human hepatic stellate cells |
| Xiao-Ping Pan, Yi-Ni Wang, Xiao-Peng Yu, Chun-Xia Zhu, Jian-Zhou Li, Wei-Bo Du, Yi-Min Zhang, Hong-Cui Cao, Yan-Hong Zhang, Dan-Hua Zhu, George C Yeoh and Lan-Juan Li |
Hangzhou, China
Author Affiliations: Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Pan XP, Wang YN, Yu XP, Zhu CX, Li JZ, Du WB, Zhang YM, Cao HC, Zhang YH, Zhu DH and Li LJ); College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China (Pan XP); Biochemistry & Molecular Biology Crawley, University of Western Australia, Western Australia 6009, Australia (Yeoh GC)
Corresponding Author: Lan-Juan Li, MD, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China (Tel/Fax: +86-571-87236759; Email: ljli@zju.edu.cn) |
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Abstract BACKGROUND: Differentiation of liver progenitor cells (LPCs) to functional hepatocytes holds great potential to develop new strategies for hepatocyte transplantation and the screening of drug-induced cytotoxicity. However, reports on the efficient and convenient hepatic differentiation of LPCs to hepatocytes are few. The present study aims to investigate the possibility of generating functional hepatocytes from LPCs in an indirect co-culture system.
METHODS: Mouse LPCs were co-cultured in Transwell plates with an immortalized human hepatic stellate cell line (HSC-Li) we previously established. The morphology, expression of hepatic markers, and functions of mouse LPC-derived cells were monitored and compared with those of conventionally cultured LPCs.
RESULTS: Co-culturing with HSC-Li cells induced differentiation of mouse LPCs into functional hepatocyte-like cells. The differentiated cells were morphologically transformed into hepatocyte-like cells 3 days after co-culture initiation. In addition, the differentiated cells expressed liver-specific genes and possessed hepatic functions, including glycogen storage, low-density lipoprotein uptake, albumin secretion, urea synthesis, and cytochrome P450 1A2 enzymatic activity.
CONCLUSIONS: Our method, which employs indirect co-culture with HSC-Li cells, can efficiently induce the differentiation of LPCs into functional hepatocytes. This finding suggests that this co-culture system can be a useful method for the efficient generation of functional hepatocytes from LPCs.
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2016, Vol. 15 
