title: Efficient generation of functional hepatocyte-like cells from mouse liver progenitor cells via indirect co-culture with immortalized human hepatic stellate cells.
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.
authors.affiliation: 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.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Pan
authors.forename: Yi-Ni
authors.initials: YN
authors.lastname: Wang
authors.forename: Xiao-Peng
authors.initials: XP
authors.lastname: Yu
authors.forename: Chun-Xia
authors.initials: CX
authors.lastname: Zhu
authors.forename: Jian-Zhou
authors.initials: JZ
authors.lastname: Li
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Du
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Hong-Cui
authors.initials: HC
authors.lastname: Cao
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Dan-Hua
authors.initials: DH
authors.lastname: Zhu
authors.forename: George C
authors.initials: GC
authors.lastname: Yeoh
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Li
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D048430:Cell Shape; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D005786:Gene Expression Regulation; D006003:Glycogen / Q000378:metabolism; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D019899:Paracrine Communication; D010641:Phenotype; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014508:Urea / Q000378:metabolism
chemical_list: D000418:Albumins; D015415:Biomarkers; D017077:Culture Media, Conditioned; D008077:Lipoproteins, LDL; D014508:Urea; D006003:Glycogen; D019388:Cytochrome P-450 CYP1A2