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Novel application of adipose-derived mesenchymal stem cells via producing antiangiogenic factor TSP-1 in lung metastatic melanoma animal model
Biologicals ( IF 1.7 ) Pub Date : 2020-10-05 , DOI: 10.1016/j.biologicals.2020.09.004
Saeid Bagheri-Mohammadi 1 , Rana Moradian-Tehrani 2 , Mahdi Noureddini 3 , Behrang Alani 2
Affiliation  

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 TSP-1 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.



中文翻译:

脂肪间充质干细胞产生抗血管生成因子TSP-1在肺转移性黑色素瘤动物模型中的新应用

人脂肪组织来源的间充质干细胞 (hAD-MSC S) 具有抑制性免疫原性,归巢于损伤、炎症和癌症部位,适用于基因治疗。PiggyBac (PB) 是一种应用于哺乳动物系统的转座子载体,可以克服其他转座子和病毒载体的一些局限性。在这项研究中,通过尾静脉注射在携带黑色素瘤小鼠的 C57BL/6 模型中评估表达血小板反应蛋白-1 (TSP-1) 的 hAD-MSCs 的治疗潜力。注射后 20 天,通过免疫组织化学 (IHC) 方法评估抗血管生成作用和活化 T 细胞的数量。通过隧道试验分析细胞凋亡值。还评估了小鼠存活率和小鼠肺中的结节数。通过蛋白质印迹,评估了 TSP-1、Bax 和 Bcl2 表达的值。结果显示 hAD-MSCs .在携带黑色素瘤的 C57BL/6 小鼠模型中,TSP-1 可以显着抑制血管生成并诱导细胞凋亡和激活 T 细胞。存活率也显着增加,结节数量减少,Bax 和 TSP-1 表达值增加,Bcl2 表达值降低。总之,我们的结果表明 hAD-MSC。TSP-1 可用作肺转移性黑色素瘤治疗的有效载体。

更新日期:2020-11-21
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