J Cancer 2020; 11(18):5345-5352. doi:10.7150/jca.38062

Research Paper

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

Chunyan Zhao1, Yu Pu1, Haidi Zhang2, Xianhua Hu2, Rendan Zhang2, Shuai He3, Qi Zhao3, Bo Mu1,2✉

1. Sicuhan Key Laboratory of Medical Imaging, Affiliated Hospital of North Sichuan Medical University 637000, Nanchong, Sichuan Province, China.
2. School of Preclinical Medicine, North Sichuan Medical University 637000, Nanchong, Sichuan Province, China.
3. Department of Clinical Medicine, North Sichuan Medical University 637000, Nanchong, Sichuan Province, China.

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Citation:
Zhao C, Pu Y, Zhang H, Hu X, Zhang R, He S, Zhao Q, Mu B. IL10-modified Human Mesenchymal Stem Cells inhibit Pancreatic Cancer growth through Angiogenesis Inhibition. J Cancer 2020; 11(18):5345-5352. doi:10.7150/jca.38062. Available from https://www.jcancer.org/v11p5345.htm

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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.

Keywords: IL10, hMSC, Angiogenesis, Pancreatic cancer