CD34+ Hematopoietic Stem Cells Mobilization, Paralleled with Multiple Cytokines Elevated in Patients with HBV-Related Acute-on-Chronic Liver Failure
- 408 Downloads
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
- 15.Yannaki E, Athanasiou E, Xagorari A, et al. G-CSF-primed hematopoietic stem cells or G-CSF per se accelerate recovery and improve survival after liver injury, predominantly by promoting endogenous repair programs. Exp Hematol. 2005;33:108–119. doi: 10.1016/j.exphem.2004.09.005.PubMedCrossRefGoogle Scholar
- 22.Liver Failure and Artificial Liver Group. Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Diseases and Artificial Liver Group, Chinese Society of Hepatology. Diagnostic and treatment guidelines for liver failure. Zhonghua Gan Zang Bing Za Zhi. 2006;14:643–646.Google Scholar
- 23.Chinese Society of Infectious Diseases and Parasitology. Chinese Society of Hepatology. Management scheme of diagnostic and therapeutic criteria of viral hepatitis. Zhonghua Gan Zang Bing Za Zhi. 2000;8:324–329.Google Scholar
- 28.Wojakowski W, Tendera M, Michalowska A, et al. Mobilization of CD34/CXCR4+, CD34/CD117+, c-met+ stem cells, and mononuclear cells expressing early cardiac, muscle, and endothelial markers into peripheral blood in patients with acute myocardial infarction. Circulation. 2004;110:3213–3220. doi: 10.1161/01.CIR.0000147609.39780.02.PubMedCrossRefGoogle Scholar
- 34.Lam SP, Luk JM, Man K, et al. Activation of interleukin-6-induced glycoprotein 130/signal transducer and activator of transcription 3 pathway in mesenchymal stem cells enhances hepatic differentiation, proliferation, and liver regeneration. Liver Transpl. 2010;16:1195–1206. doi: 10.1002/lt.22136.PubMedCrossRefGoogle Scholar