IL10-modified Human Mesenchymal Stem Cells inhibit Pancreatic Cancer growth through Angiogenesis Inhibition.

In the present study, we constructed the recombinant plasmid IL10-PEGFP-C1 and successfully transfected into human mesenchymal stem cells. After culturing for 72 h, the levels of IL6 and TNF-alpha in the supernatant of the MSCs-IL10 group were significantly lower than the vector group and the control group (17.6 +/- 0.68vs73.8 +/- 0.8 and 74.4 +/- 1.5) mu g/L and (65.05 +/- 3.8 vs 203.2 +/- 2.4 and 201.3 +/- 3.7) mu g/L, respectively (p < 0.001) .The animal experiments showed that the volume of subcutaneous tumors in the MSCs-IL10 group in vivo was a significantly less level compared to that in MSC control and the blank control groups (76.84 +/- 20.11) mm(3) vs (518. 344 +/- 48.66) mm(3), (576.99 +/- 49.88) mm(3), (P < 0.05) and they have a longer life time. Further we found the mass concentrations of IL6 and TNF-alpha in the blood serum of MSC-IL10 group were lower than the vector group and the control group (64.42 +/- 10.9 vsl 20.83 +/- 15.52 and 122.65 +/- 13.71) and (40.05 +/- 5.63 vs 126.78 +/- 1.89 and 105.83 +/- 2.16) mu g/L respectively (p < 0.001). CD31 immunohistochemistry and alginate encapsulation experiments showed tumor angiogenesis were inhibited in MSCs-IL10 group in comparison to the control and vector group (P < 0.001), FITC-labeled dextran intake was also lower than the other groups (P < 0.01). Collectively, this study suggested IL10 could inhibit the growth of the transplanted tumor in vivo and prolong survival of mice, and the primary mechanism may be the indirect inhibition of pro-inflammatory cytokines IL6 and TNF-alpha secretion and tumor angiogenesis formation.