Study on murine Heps hepatoma tissue after mesenchymal stem cells inoculation / 国际肿瘤学杂志

ABSTRACT

Objective To observe the local immue response and changes of angiogenic factors of tumor cells in Heps-bearing mice after mesenchymal stem cell (MSC) are administrated. And to explore the feasibility and safety of MSC for liver tumors therapy. Methods MSC were obtained through adherent culture method. Phe-notypes of MSC were analyzed by flow cytometry. MSC were labeled with DAPI in vitro. 54 Mice of 8 weeks of age with subcutaneously transplanted liver carcinomas were developed randomly. When the maximal diameters of the tumor reached 0.5 - 0.8cm, they were divided into three groups randomly MSC group, DAPI group and NS control group. 2 × 10~6 MSC and MSC marked by DAPI were administrated into the mice right rear back tumor tissue. The survival time of the tumor-bearing mice was recorded and the mean survival time was calculated. Immunohistochemical staining was performed to count CD4~+ T cells and CD8~+ T cells in the local tumor,as well as to examine the expression of vascular endothelial growth factor ( VEGF) in tumor cells. Results In the MSC group,the mean survival time was 45 d (95%CI;33 ～56 d) ,in the NS control group, the mean survival time was 33 d ( 95%CI 28 ～ 37 d). There was a statistical significance in the difference between them ( P < 0.05). Immunohistochemical staining results showed as follow the number of CD4~+ T cells and CD8~+ T cells in the MSC group decreased significantly in comparison with the NS control group at early stage. The expression of VEGF also decreased obviously in comparison with the NS control group and induced tumor cells necrosis at late stage. The survival time of MSC group was prolonged. Conclusion MSC can engraft in Heps-bearing tumor tissue, and inhibit T lymphocyte cellular immunity at early stage. It can reduce the number of CD4~+ T cells and CD8~+ T cells and promote tumor growth. MSC can down regulate VEGF expression and induce tumor cells necrosis at late stage. By this way,it can prolong the survival time of Heps-bearing mice.