Characterization of CD133+ parenchymal cells in the liver: histology and culture

World J Gastroenterol. 2009 Oct 21;15(39):4896-906. doi: 10.3748/wjg.15.4896.


Aim: To reveal the characteristics of CD133(+) cells in the liver.

Methods: This study examined the histological characteristics of CD133(+) cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133(+) cells derived from human hepatocellular carcinoma (HCC) or cholangiocarcinoma cell lines.

Results: Immunostaining revealed constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133(+)/CK19(+)/HepPar-1(-). A small number of CD133(+)/CK19(-)/HepPar-1(+) cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC (HuH7, PLC5 and HepG2) and two cholangiocarcinoma cell lines (HuCCT1 and CCKS1). Fluorescence-activated cell sorting (FACS) revealed that CD133(+) and CD133(-) cells derived from HuH7 and HuCCT1 cells similarly produced CD133(+) and CD133(-) cells during subculture. To examine the relationship between CD133(+) cells and the side population (SP) phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133(+)/CD133(-) cells were almost identical in the SP and non-SP in HuH7. In addition, four different cellular populations (SP/CD133(+), SP/CD133(-), non-SP/CD133(+), and non-SP/CD133(-)) could similarly produce CD133(+) and CD133(-) cells during subculture.

Conclusion: This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines.

MeSH terms

  • AC133 Antigen
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / immunology*
  • Bile Duct Neoplasms / pathology
  • Bile Ducts, Intrahepatic / immunology*
  • Bile Ducts, Intrahepatic / pathology
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Separation
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / immunology*
  • Cholangiocarcinoma / pathology
  • Epithelial Cells / immunology*
  • Epithelial Cells / pathology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Immunohistochemistry
  • Keratin-19 / metabolism
  • Liver / immunology*
  • Liver / pathology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Peptides / genetics
  • Peptides / metabolism*
  • Phenotype
  • Polymerase Chain Reaction
  • RNA, Messenger / metabolism
  • Time Factors
  • alpha-Fetoproteins / metabolism


  • AC133 Antigen
  • AFP protein, human
  • Antigens, CD
  • Glycoproteins
  • Keratin-19
  • PROM1 protein, human
  • Peptides
  • RNA, Messenger
  • alpha-Fetoproteins