Novel immortalized human fetal liver cell line, cBAL111, has the potential to differentiate into functional hepatocytes

Tanja Deurholt, Niek P van Til, Aniska A Chhatta, Lysbeth ten Bloemendaal, Ruth Schwartlander, Catherine Payne, John N Plevris, Igor M Sauer, Robert Afm Chamuleau, Ronald Pj Oude Elferink, Jurgen Seppen, Ruurdtje Hoekstra*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background
A clonal cell line that combines both stable hepatic function and proliferation capacity is desirable for in vitro applications that depend on hepatic function, such as pharmacological or toxicological assays and bioartificial liver systems. Here we describe the generation and characterization of a clonal human cell line for in vitro hepatocyte applications.

Results
Cell clones derived from human fetal liver cells were immortalized by over-expression of telomerase reverse transcriptase. The resulting cell line, cBAL111, displayed hepatic functionality similar to the parental cells prior to immortalization, and did not grow in soft agar. Cell line cBAL111 expressed markers of immature hepatocytes, like glutathione S transferase and cytokeratin 19, as well as progenitor cell marker CD146 and was negative for lidocaine elimination. On the other hand, the cBAL111 cells produced urea, albumin and cytokeratin 18 and eliminated galactose. In contrast to hepatic cell lines NKNT-3 and HepG2, all hepatic functions were expressed in cBAL111, although there was considerable variation in their levels compared with primary mature hepatocytes. When transplanted in the spleen of immunodeficient mice, cBAL111 engrafted into the liver and partly differentiated into hepatocytes showing expression of human albumin and carbamoylphosphate synthetase without signs of cell fusion.

Conclusion
This novel liver cell line has the potential to differentiate into mature hepatocytes to be used for in vitro hepatocyte applications.
Original languageEnglish
Article number89
Number of pages15
JournalBMC Biotechnology
Volume9
DOIs
Publication statusPublished - 2009

Keywords

  • Animals
  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Line
  • Fetus
  • Flow Cytometry
  • Hepatocytes
  • Humans
  • Liver
  • Mice
  • Telomerase

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