IL10-modified human mesenchymal stem cells inhibit pancreatic cancer growth through angiogenesis inhibition

Abstract

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-α 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) µg/L and (65.05 ± 3.8 vs 203.2 ± 2.4 and 201.3 ± 3.7) µg/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) mm3 vs (518. 344 ± 48.66) mm3, (576.99± 49.88) mm3, (P < 0. 05) and they have a longer life time. Further we found the mass concentrations of IL6 and TNF-α in the blood serum of MSC-IL10 group were lower than the vector group and the control group (64.42 ± 10.9 vs120.83 ± 15.52 and 122.65 ± 13.71) and (40.05 ± 5.63 vs 126.78 ±1.89 and 105.83 ± 2.16) µg/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-α secretion and tumor angiogenesis formation.