| Backgrounds Recently the research in the field of liver stem cells has made striking progress. At present it is generally accepted that hepatic stem cells do exist in the liver, they are quiecent at normal conditions, while begin to activate, expand and differentiate into hepatocytes to regenerate the livers suffered to serious damage. In 1999 Petersen et al found bone marrow cells could differentiate into hepatic oval cells and/or hepatocytes by cross-sex bone marrow transplantation in rats, later many researchers also obtained similar results in murines and human. Therefore, it is presented that not only were hepatic stem cells endogenously originated from the Hering canals of livers, but also from bone marrow cells. With the ability of self-maintenance as well as clonal expansion and the potential of differentiating into hepatocytes and biliary ducts, hepatic stem cells may have important clinical implications in treating serious liver diseases such as cirrhosis and hepatic failure, especially for hepatic stem cells derived from bone marrow which are available to obtain and have no immunological rejection reaction. However, there are a lot of questions required to be resolved before the clilical application of hepatic stem cells. First of all the mechanism responsible for activation , expansion and differentiation of hepatic stem cells must be defined. Dure tothe origin and the accurate location of hepatic stern cells are still unclear, oval cells that have been comparatively clearly difined and described as the progeny of hepatic stem cells are widely used to the research of identifying the regulatory mechanism. Oval cells are small in size (approximately 10um), with a large nucleus-to-cytoplasm ratio and an oval-shaped nucleus, and can differentiate into hepatocytes and bile duct in vitro and vivo. These cells express the specific markers of both hepatocytes and bile epithelium including albumine, alpha-fetoprotein(AFP), cytokeratin-18(CK-18), cytokeratin-19 (CK-19), OV-6 and so on. Recently many investigators have showed that the markers special for haematopoietic stern cells(HSC) including Thy-1, c-Kit and CD-34 were also expressed by oval cells, which further surpported that hepatic stem cells may originate from bone marrow. To elucidate the regulatory mechanism responsible for oval cells will facilitate the establishment of in vitro models to investigate oval cell biology, help establish links, if any, between the bone marrow-derived liver stem cells and oval cells, and be useful for clinical application of hepatic stem cells. Previous studies have confirmed that plenty of cytokines and growth factors involved in the biology of oval cells, which included hepatocyte growth factor(HGF), acidic fibroblast growth factor(aFGF), transforming growth factor alpha(TGF-a), transforming growth factor-beta(TGF-(5), tumour necrosis factor-alpha(TNF-a), interleukin-6(IL-6), stem cell factor(SCF), urosine plasminogen activator (UFA) and so on. Some researchers have successively isolated oval cells from livers of murines, followed by culturing them in vitro using some growth factors such as HGF and aFGF, and obtained some heptocyte-like cells which had partial function of hepatocytes such as synthesize urea and glycogen. Lately investigations using suppression subtractive hybridzation(SSH) cloned genes associated with oval cells proliferating and demonstrated that the gene network connected to interferon-gamma (IFN-y) may play an important role in oval cells. It is known that IFN-y isn't a mitogen to hepatocytes, so it is diserved to be explored whether it can enhance the expansion and differentiation of oval cells. Therefore, using RT-PCR analysis the transcripts for interferon-gamma receptor alpha (IFN-yRa), intercellular adhesive molecule-1 (1CAM-1) and alpha-fetoprotein (AFP) were detected in the 2-AAF/PH model, and the relationship between the expression of IFN-yRa aswell as ICAM-1 and the proliferation and differentiation of oval cells were further investigated.Methods Male wistar rats weighi... |
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