| Objective: To investigate the inhibitory effect of human liver-derived stem cells(HLSCs)on colorectal cancer liver metastasis(CRLM)and its mechanism,we examined the changes of liver function in a mouse model of colon cancer liver metastasis after HLSCs treatment,compared the levels of immune cells in spleen and bone marrow of different groups of mice,and quantified the tumor-associated mediators in liver tissue.We investigated whether HLSCs have a certain inhibitory effect on colon cancer liver metastasis and its related mechanism by examining the changes of liver function,comparing the immune cell contents in spleen and bone marrow of different groups of mice,and quantifying the tumor-related mediators in liver tissues of mice.Methods: Thirty male,SPF-grade,6-8-week-old C57BL/6 mice were randomly assigned to the blank control group(group N),model control group(group M)and HLSCs treatment group(group S)by random number method.HLSCs were transplanted intraperitoneally twice a week to group S,while equal amounts of PBS solution were injected to group N and group M.After 2 weeks of intervention,the growth of liver metastases was observed in M and S groups,and the serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured in the three groups,and the bone marrow-derived stem cells(Myeloid)in the mice were detected by flow cytometry.The changes of immune cells such as Myeloid-derived suppressor cells(MDSC)in bone marrow and T lymphocytes and macrophages in spleen of mice were detected by flow cytometry,and the changes of VEGF and MMP2 expression were detected by immunohistochemistry in liver sections of mice.Results: Compared with the three groups,the livers of the N group showed bright red color and smooth surface,while the livers of the M group were larger and tumor infiltration could be found;compared with the M group,the liver tumor infiltration of the S group was significantly reduced;the differences in serum ALT and AST levels,MDSC in bone marrow and CD8+ T lymphocytes and macrophages in spleen were statistically significant.The differences were statistically significant.Compared with group N,mice in group M showed significantly higher serum ALT and AST,while mice in group S showed significantly lower serum ALT,AST and MDSC in bone marrow tissue than those in group M.The levels of CD8+ T lymphocytes and M1 macrophages in spleen tissue were significantly higher than those in group M(p-value <0.05).The expression levels of VEGF and MMP2 in the M group were significantly higher than those in the N group,while the expression levels of VEGF and MMP2 in the S group were significantly lower than those in the M group,with P-values <0.05.Conclusion: In this study,the levels of macrophages,T-lymphocytes and MDSC-related immune cells in spleen and bone marrow of mice in different groups were successfully detected by flow cytometry,and HLSCs were found to increase the levels of CD8+ T-lymphocytes and M1-type macrophages in spleen and significantly decrease the levels of MDSC in bone marrow to exert the inhibitory effect on CRLM.This study provides a theoretical basis for the inhibition of CRLM by HLSCs,and provides new research ideas and directions for the immunotherapy of patients with CRLM. |
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