表达sFlt-1的小鼠骨髓间充质干细胞介导的抗肿瘤作用研究

Anti-tumor therapy based on the mouse mesenchymal stem cells genetically engineered to express soluble sFlt-1

目的间充质干细胞(mesenchymal stem cells,MSCs)是存在于骨髓中的一种具有多向分化潜能和很强增殖能力的细胞。经静脉输注的MSCs能特异性地聚集于新生组织,如伤口和肿瘤等,本实验将MSCs作为基因治疗靶向载体,研究其在肿瘤组织内的抗血管作用。方法从雄性小鼠股骨骨髓中分离和培养MSCs,用流式细胞仪检测CD34、CD29、CD44的表达。再用sFlt-1(VEGF-R1)重组腺病毒感染后,给荷瘤小鼠静脉注射。结果间充质干细胞聚集在肿瘤内表达sFlt-1,使得肿瘤血管生成受抑制、肿瘤细胞凋亡增加、肺转移灶减小、生存时间延长。结论本研究表明,MSCs作为基因的运载工具在抗肿瘤领域可能有一定的应用价值。

Objective Biology and therapy of mesenchymal stem celI（MSC） is one of quickly growing areas of investigation that has drawn intense scrutiny from the biomedical research community. As a vehicle, MSCs were found to preferably go to those sites of tumorigenesis and wound healing. Here we described mouse MSCs specifically delivering recombinant adenoviruses which express mouse soluble FIt-1（VEGF-R1） into tumor. Methods The MSCs were isolated from hone marrow of male mouse and passaged in L-DMEM with 10% FBS. After the identification of MSC by fibroblast-like appearance and flow cytometry （CD34^- , CD29^＋ ,CD44^＋ ）. they were infected by recombinant adenoviruses which express sFh-1 and tail vein infused for the purpose of reaching the metastasis and blocking the angiogenesis. Results The MSCs were found to preferentially home into metastases. The prolonged survival rate, decreased metastasis and angiogenesis as well as increased apoptosis were detected. Conclusion MSC has the potential to be a promising vehicle in targeting system of cancer gene therapy.