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Deficient Proliferation of Bone Marrow-Derived Mesenchymal Stem Cells in Patients with Chronic Hepatitis B Viral Infections and Cirrhosis of the Liver

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Abstract

In this study, we determined whether the proliferation of bone marrow-derived mesenchymal stem cells (MSCs) is impaired in patients with chronic hepatitis B viral infection and cirrhosis of the liver. MSCs from 15 patients with chronic hepatitis B and cirrhosis of the liver (CIR-MSCs) and 11 normal donors (ND-MSCs) were collected and characterized in vitro. CIR-MSCs displayed an intact immunophenotype. The percentage of S-phase nuclei in CIR-MSCs (4.34%), however, was significantly lower than that in ND-MSCs (P < 0.001), indicating impaired proliferation of CIR-MSCs. Growth factor receptor expression (e.g., IGF1, PDGFα, and PDGFβ) on the surface of CIR-MSCs decreased compared to that on ND-MSCs (P < 0.03). We found no evidence that CIR-MSCs were infected with the hepatitis B virus (HBV). Deficient proliferation of CIR-MSCs may result from the decreased expression of growth factor receptors and unbalanced production of cytokines in patients with HBV infection. Our results indicate that autologous MSCs of patients with chronic hepatitis B and cirrhosis of the liver may not be suitable for therapeutic purposes.

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Abbreviations

MSCs:

Bone marrow-derived mesenchymal stem cells

HBV:

Hepatitis B virus

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

PL:

Platelet-enriched plasma lysate

CIR-MSCs:

Bone marrow-derived mesenchymal stem cells of patients with chronic hepatitis B virus infection and liver cirrhosis

ND-MSCs:

Bone marrow-derived mesenchymal stem cells of normal donors

EDTA:

Ethylenediamine tetraacetic acid

HB:

Hepatitis B

RT-PCR:

Reverse transcription-polymerase chain reaction

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Acknowledgments

This work was supported by the Science and Technology Development Fund of Guangdong (2005A30201007), the natural science fund of Guangdong (06021343), and the research fund for the doctoral program of the Ministry of Education (20070558259). We thank Professor Lin Yang from the Department of Infectious Diseases’ Laboratory at the 3rd affiliated hospital of Sun Yat-Sen University for assistance with detecting HBV infections.

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Correspondence to Rui-Yun Xu.

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Yue-Si Zhong and Nan Lin have contributed equally to this work.

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Zhong, YS., Lin, N., Deng, MH. et al. Deficient Proliferation of Bone Marrow-Derived Mesenchymal Stem Cells in Patients with Chronic Hepatitis B Viral Infections and Cirrhosis of the Liver. Dig Dis Sci 55, 438–445 (2010). https://doi.org/10.1007/s10620-009-0733-4

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