Epithelial cells with hepatobiliary phenotype: Is it another stem cell candidate for healthy adult human liver?

Abstract

AIM:To investigate the presence and role of liver epithelial cells in the healthy human adult liver. METHODS:Fifteen days after human hepatocyte primary culture, epithelial like cells emerged and started proliferating. Cell colonies were isolated and subcultured for more than 160 d under specific culture conditions. Cells were analyzed for each passage using immunofluorescence, flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:Flow cytometry analysis demonstrated that liver epithelial cells expressed common markers fo r h e p a t i c a n d s t e m c e l l s s u c h a s C D 9 0 , C D 4 4 and CD29 but were negative for CD34 and CD117. Using immunofluorescence we demonstrated that liver epithelial cells expressed not only immature (α-fetoprotein) but also differentiated hepatocyte (albumin and CK-18) and biliary markers (CK-7 and 19), whereas they were negative for OV-6. RT-PCR analysis confirmed immunofluorescence data and revealed that liver epithelial cells did not express mature hepatocyte markers such as CYP2B6, CYP3A4 and tyrosine amino-transferase. Purified liver epithelial cells were transplanted into SCID mice. One month after transplantation, albumin positive cell foci were detected in the recipient mouse parenchyma.CONCLUSION: According to their immature and bipotential phenotype, liver epithelial cells might represent a pool of precursors in the healthy human adult liver other than oval cells.

Cytokeratins of the Liver and Intestine Epithelial Cells During Development and Disease

“…Studies have attempted to define the nature and position of progenitor cells within the liver in a variety of ways. This has included study of animal models of liver diseases, embryological human livers in cell culture and in vivo (Nava, Westgren et al 2005) (Nowak et al 2005) and adult human livers in cell culture (Herrera, Bruno et al 2006) (Khuu, Najimi et al 2007) and in vivo (Chatzipantelis, Lazaris et al 2006). In our own studies we demonstrated that in vitro expanded human fetal liver progenitor cells express CK18, CK8 and some CK19 (Figure 1).…”

Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME

“…Moreover, when cultured in rotary BAL, HLSCs acquired the expression of liver-specific transcription factors such as HFN-4 and C/EBP (Fonsato et al 2010). The presence of a progenitor/stem cell population in the adult liver was confirmed by Khuu et al (2007) that describe an epithelial cell population with characteristics similar to HLSC. However, this cell population is more engaged in the hepatocytic lineage than HLSC (Khuu et al 2007).…”

“…The presence of a progenitor/stem cell population in the adult liver was confirmed by Khuu et al (2007) that describe an epithelial cell population with characteristics similar to HLSC. However, this cell population is more engaged in the hepatocytic lineage than HLSC (Khuu et al 2007). …”

In Vitro Differentiated Adult Human Liver Progenitor Cells Display Mature Hepatic Metabolic Functions: A Potential Tool for in Vitro Pharmacotoxicological Testing

“…for instance oval cells (31), are difficult to isolate and to maintain longer in vitro (9, 16,18). Extrahepatic stem/ However, the technique faces various problems, such as lack of supply due to organ shortage, poor proliferation progenitor cells, such as mesenchymal phenotype, show good potential for proliferation and are easy to manipucapacity of mature hepatocytes, poor resistance to cryostorage, and limited durability of the metabolic effect late in vitro, whereas their functional differentiation capability remains quite variable and incomplete (5,8,19, (29).…”