PMID- 27020634 OWN - NLM STAT- MEDLINE DCOM- 20170103 LR - 20191113 IS - 1499-3872 (Print) VI - 15 IP - 2 DP - 2016 Apr TI - Efficient generation of functional hepatocyte-like cells from mouse liver progenitor cells via indirect co-culture with immortalized human hepatic stellate cells. PG - 173-9 AB - 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. FAU - Pan, Xiao-Ping AU - Pan XP AD - 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. ljli@zju.edu.cn. FAU - Wang, Yi-Ni AU - Wang YN FAU - Yu, Xiao-Peng AU - Yu XP FAU - Zhu, Chun-Xia AU - Zhu CX FAU - Li, Jian-Zhou AU - Li JZ FAU - Du, Wei-Bo AU - Du WB FAU - Zhang, Yi-Min AU - Zhang YM FAU - Cao, Hong-Cui AU - Cao HC FAU - Zhang, Yan-Hong AU - Zhang YH FAU - Zhu, Dan-Hua AU - Zhu DH FAU - Yeoh, George C AU - Yeoh GC FAU - Li, Lan-Juan AU - Li LJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Singapore TA - Hepatobiliary Pancreat Dis Int JT - Hepatobiliary & pancreatic diseases international : HBPD INT JID - 101151457 RN - 0 (Albumins) RN - 0 (Biomarkers) RN - 0 (Culture Media, Conditioned) RN - 0 (Lipoproteins, LDL) RN - 8W8T17847W (Urea) RN - 9005-79-2 (Glycogen) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A2) SB - IM MH - Albumins/metabolism MH - Animals MH - Biomarkers/metabolism MH - *Cell Differentiation MH - Cell Line MH - Cell Shape MH - Coculture Techniques MH - Culture Media, Conditioned/metabolism MH - Cytochrome P-450 CYP1A2/metabolism MH - Gene Expression Regulation MH - Glycogen/metabolism MH - Hepatic Stellate Cells/*metabolism MH - Hepatocytes/*metabolism MH - Humans MH - Lipoproteins, LDL/metabolism MH - Liver/cytology/*metabolism MH - Male MH - Mice, Inbred C57BL MH - *Paracrine Communication MH - Phenotype MH - Stem Cells/*metabolism MH - Time Factors MH - Urea/metabolism EDAT- 2016/03/30 06:00 MHDA- 2017/01/04 06:00 CRDT- 2016/03/30 06:00 PHST- 2016/03/30 06:00 [entrez] PHST- 2016/03/30 06:00 [pubmed] PHST- 2017/01/04 06:00 [medline] AID - S1499-3872(16)60074-7 [pii] AID - 10.1016/s1499-3872(16)60074-7 [doi] PST - ppublish SO - Hepatobiliary Pancreat Dis Int. 2016 Apr;15(2):173-9. doi: 10.1016/s1499-3872(16)60074-7.