title: Induction of highly functional hepatocytes from human umbilical cord mesenchymal stem cells by HNF4α transduction.
abstract: OBJECTIVE
  To investigate the differentiation potential of human umbilical mesenchymal stem cells (HuMSCs) and the key factors that facilitate hepatic differentiation.
  
  
  METHODS
  HuMSCs were induced to become hepatocyte-like cells according to a previously published protocol. The differentiation status of the hepatocyte-like cells was examined by observing the morphological changes under an inverted microscope and by immunofluorescence analysis. Hepatocyte nuclear factor 4 alpha (HNF4α) overexpression was achieved by plasmid transfection of the hepatocyte-like cells. The expression of proteins and genes of interest was then examined by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods.
  
  
  RESULTS
  Our results demonstrated that HuMSCs can easily be induced into hepatocyte-like cells using a published differentiation protocol. The overexpression of HNF4α in the induced HuMSCs significantly enhanced the expression levels of hepatic-specific proteins and genes. HNF4α overexpression may be associated with liver-enriched transcription factor networks and the Wnt/β-Catenin pathway.
  
  
  CONCLUSIONS
  The overexpression of HNF4α improves the hepatic differentiation of HuMSCs and is a simple way to improve cellular sources for clinical applications.
authors.affiliation: Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Jiao Tong University, Shanghai, China; Department of General Surgery, Nanjing Hospital Affiliated to NanJing Medical University, Nanjing, China.
authors.forename: Hualian
authors.initials: H
authors.lastname: Hang
authors.affiliation: Department of General Surgery, Nanjing Hospital Affiliated to NanJing Medical University, Nanjing, China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Nanjing Hospital Affiliated to NanJing Medical University, Nanjing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Nanjing Hospital Affiliated to NanJing Medical University, Nanjing, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Jiao Tong University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xia
authors.affiliation: Department of General Surgery, Nanjing Hospital Affiliated to NanJing Medical University, Nanjing, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Bian
mesh_terms: D028341:Activins / Q000494:pharmacology; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology; D010957:Plasmids; D012643:Selenium / Q000494:pharmacology; D015398:Signal Transduction; D014162:Transfection; D014168:Transferrin / Q000494:pharmacology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D007328:Insulin; D014168:Transferrin; D051153:Wnt Proteins; C422405:activin A; D051176:beta Catenin; D028341:Activins; D009536:Niacinamide; D004815:Epidermal Growth Factor; D012643:Selenium