Chinese Journal of Tissue Engineering Research ›› 2010, Vol. 14 ›› Issue (10): 1769-1774.doi: 10.3969/j.issn.1673-8225.2010.10.012

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Rat bone marrow mesenchymal stem cells induce hepatic stellate cells apoptosis in vivo

Lin Nan1, Xie Shu-jie1, Pan Wei-dong1, Hu Kun-peng1, Chen Si1, Chong Yu-tian2, Xiang Peng3, Xu Rui-yun1   

  1. 1Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou   510630, Guangdong Province, China;
    2Department of Infectious Disease, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou   510630, Guangdong Province, China;
    3Research Center of Stem Cells and Tissue Engineering, Sun Yat-sen University, Guangzhou   510080, Guangdong Province, China
  • Online:2010-03-05 Published:2010-03-05
  • Contact: Xu Rui-yun, Master, Professor, Doctoral supervisor, Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China drxuruiyun@gmail. com
  • About author:Lin Nan, Doctor, Attending physician, Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China siabc83@163.com Xie Shu-jie, Studying for master’s degree, Department of Hepatobiliary Surgery, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China Jackyx1983@yahoo.cn Lin Nan and Xie Shu-jie contributed equally to this artide.
  • Supported by:

    the Great Science and Technology Specific Foundation of Department of Science and Technology of Guangdong Province, No. 2005A30201007*;
    the Natural Science Foundation of Guangdong Province, No. 8151008901 000086*;
    the Youth Teacher Foundation of Medical Sciences of Sun Yat-sen University, No. 3171916;
    Science and Technology Plan Project of Guangdong Province, No. 2006B36005004*

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Abstract:

BACKGROUND: It is reported that bone marrow mesenchymal stem cell (BMSC) transplantation might be a promising treatment for liver fibrosis. But the mechanism is still unclear.

OBJECTIVE: To observe the hepatic stellate cells apoptosis induced by BMSC transplantation, and to study the mechanism of BMSC in treating hepatic fibrosis in vivo.

METHODS: CCl4 subcutaneous injection was performed to induce rat liver fibrosis. After 8 weeks of CCl4 injection, 20 rats which underwent successful model establishment were randomly divided into experimental group and control group, 10 in each group. The experimental group received MSC transplantation via tail vein injection, and the control group were given DMEM instead. The rats were killed and the livers were harvested at three time point, the day of MSC transplantation, 3 days after transplantation, and 7 days after transplantation. The hydroxyproline content was detected by HE and Masson staining, and the expression changes of α-smooth muscle actin (α-SMA) proteins were determined using immunohistochemistry. The apoptosis of hepatic stellate cells were determined by α-SMA and TUNEL (terminal dUTP nick-end labeling) dual-staining.

RESULTS AND CONCLUSION: After 8 weeks of CCl4 injection, the hydroxyproline content increased and histology indicated progress of liver fibrosis. At 7 days after MSC transplantation, the hydroxyproline in the liver was decreased, and the liver fibrosis was alleviated in the experimental group but aggravated in the control group. Immunohistochemistry indicated that α-SMA positive cells were increased at 8 weeks after CCl4 injection. At day 7 after transplantation, α-SMA positive cells in the experimental group were significantly less than control group (P < 0.05). At 3 days after transplantation, the hepatic stellate cells apoptosis in the experimental group was significantly aggravated compared with control group (P < 0.05). This suggested that MSC transplant was an effective treatment for liver fibrosis. MSC inducing hepatic stellate cells apoptosis may be one of the mechanisms.

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