Introduction Bone marrow-derived stem cells (BMSCs) are pluripotent cells that can be mobilised into circulation and recruited to sites of inflammation where they promote local tissue repair. Therefore, the present work was designed to study circulating BM-derived hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) and serum levels of stem cell factor (SCF), a stem cell mobilising factor, in patients with chronic hepatitis C (CHC) in relation to hepatic proliferation and fibrosis.
Methods Thirty treatment-naïve patients with CHC and 15 healthy subjects were included in the study. The BM-derived HSCs and MSCs cells in fresh blood samples were identified as CD34+CD45+CD117+ and CD34-CD45-CD106+ cells respectively using flow cytometric assay. Serum SCF levels were measured using an enzyme linked immunosorbant assaykit. Liver biopsies were examined to assess METAVIR histological activity grade and fibrosis stage and steatosis grade. Immunohistochemical staining of liver specimens was done using monoclonal antibodies against cytokeratin (CK)7 for detection of hepatic progenitor cells (HPCs), Ki-67 as proliferation marker and a-smooth muscle actin (a-SMA) for identification of activated hepatic stellate cells (HpSCs).
Results Patients with CHC showed significant increases in the percentages of HSCs and MSCs in peripheral blood and serum SCF levels compared with healthy subjects (P < 0.05). Numerous CK7+ HPCs were detected mostly lining primitive bile ducts or as individual positive cells in the portal tracts. Hepatic proliferative activity evidenced as nuclear positivity for Ki-67, was observed in proliferated ductal profiles in portal tracts and within hepatocytes and directly correlated with HPC expansion. Based on the percentages of BMSCs in peripheral blood, patients with CHC were distinguished into two types of patients: “mobilizers” and “non-mobilizers”. BMSC mobilizers showed a significant increase in serum SCF levels and significant decreases in HPC expansion, hepatic proliferative activity, serum levels of aminotransferases, histological activity grade, fibrosis stage and a-SMA expression compared with BMSC non-mobilizers (P < 0.01).
Conclusion Chronic HCV infection is associated with mobilisation of BMSCs from the BM into the circulation in parallel with an increased production of SCF, particularly when HPC activation and hepatic proliferative activity are impaired. Although the mobilised BMSCs are not sufficient to bring about hepatic repopulation, they may play an important role in limiting hepatic necroinflammation and fibrosis in HCV-induced liver damage.
Disclosure of Interest None Declared
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