Novel application of adipose-derived mesenchymal stem cells via producing antiangiogenic factor TSP-1 in lung metastatic melanoma animal model

被引:16
作者
Bagheri-Mohammadi, Saeid [1 ,2 ,3 ]
Moradian-Tehrani, Rana [3 ]
Noureddini, Mahdi [2 ,3 ]
Alani, Behrang [3 ]
机构
[1] Shahid Beheshti Univ Med Sci, Sch Med, Dept Physiol & Neurophysiol, Res Ctr, Tehran, Iran
[2] Kashan Univ Med Sci, Fac Med, Dept Physiol, Kashan, Iran
[3] Kashan Univ Med Sci, Fac Med, Dept Appl Cell Sci, Kashan, Iran
关键词
Gene therapy; Melanoma; Mesenchymal stem cells; PiggyBac; Thrombospondin-1; GENE-THERAPY; CANCER; EXPRESSION; THROMBOSPONDIN-1; PIGGYBAC; DELIVERY; VARIANT; FUTURE;
D O I
10.1016/j.biologicals.2020.09.004
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Human adipose tissue derived mesenchymal stem cells (hAD-MSCS) with suppressive immunogenicity, homing to injury, inflammatory, and cancer sites can be suitable for gene therapy. PiggyBac (PB) is a type of transposon vector applied in mammalian systems and could overcome some limitations of other transposon and viral vectors. In this study, the therapeutic potential hAD-MSCs expressing thrombospondin-1 (TSP-1) is assessed through tail vein injection in C57BL/6 models bearing melanoma mice. Twenty days after injection, antiangiogenic effects and number of activated T. cells are assessed by Immunohistochemistry (IHC) method. Apoptosis value is analyzed by tunnel assay. Mice survival and numbers of nodules in mice lungs also are assessed. By western blotting, value of TSP-1, Bax and Bcl2 expression are assessed. The result revealed that hAD-MSCs.TSP-1 can inhibit angiogenesis and induce apoptosis and activated T. cells in a significant manner in C57BL/6 mice models bearing melanoma. Survival also significantly increased and number of nodules decreased, value of Bax and TSP1 expression increased and value of Bcl2 expression decreased. In conclusion, our result showed that hAD-MSC. TSP-1 can be applied as an effective delivery vehicle in lung metastatic melanoma therapy.
引用
收藏
页码:9 / 18
页数:10
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