CD34+ Hematopoietic Stem Cells Mobilization, Paralleled with Multiple Cytokines Elevated in Patients with HBV-Related Acute-on-Chronic Liver Failure
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Recent studies indicate that bone marrow (BM)-derived stem cells contribute to liver regeneration. But limited information is available on the dynamic and mechanisms of mobilization of BM-derived hematopoietic stem cells (HSCs) after acute-on-chronic liver failure (ACLF).
The purpose of this study was to assess the mobilization of BM-derived CD34+ HSCs in ACLF patients, and elucidate the association of stress-induced cytokines in HSCs mobilization and/or liver repair in ACLF patients.
Thirty patients with HBV-related ACLF, 30 patients undergoing chronic hepatitis B, and 20 healthy controls were enrolled. The percentages of peripheral blood CD34+ cells were determined by two-color flow cytometry. The hepatic commitment of mobilized CD34+ cells was investigated by RT-PCR. The serum levels of stress-induced cytokines were determined by enzyme-linked immunosorbent assays.
A significant increase of circulating CD34+ cells was observed in ACLF patients. RT-PCR analyses showed that the mobilized CD34+ cells expressed both CD34 mRNA and liver-specific markers including cytokeratin 19 and α-fetoprotein. In parallel with mobilization of BM-derived CD34+ cells, elevated serum levels of hepatocyte growth factor, interleukin-6, stem cell factor, granulocyte colony-stimulating factor and matrix metalloproteinase 9 were observed in ACLF patients.
We demonstrated that ACLF led to mobilization of CD34+ cells, which had a hepatic differentiation potential.
KeywordsHematopoietic stem cell Acute-on-chronic liver failure Mobilization Liver regeneration
The research was supported by grants from the National Natural Science Foundation of China (No: 30972625), the 12th Five-Year National Science and Technology Major Project for Infectious Diseases (No: 2012ZX10002004-005), and the 12th Five-Year Grand Project of PLA (No: BWS11J075). We thank Susan Wong and Ning Zhi from Hematology Branch/National Institutes of Health in Bethesda, MD, USA for help in preparing the manuscript.
Conflict of interest
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