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In Vivo therapeutic potential of mesenchymal stem cell-derived extracellular vesicles with optical imaging reporter in tumor mice model

机译:光学成像报告基因在肿瘤小鼠模型中间充质干细胞源性细胞外囊泡的体内治疗潜力

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摘要

Mesenchymal stem cells (MSCs) can be used as a therapeutic armor for cancer. Extracellular vesicles (EVs) from MSCs have been evaluated for anticancer effects. In vivo targeting of EVs to the tumor is an essential requirement for successful therapy. Therefore, non-invasive methods of monitoring EVs in animal models are crucial for developing EV-based cancer therapies. The present study to develop bioluminescent EVs using Renilla luciferase (Rluc)-expressing MSCs. The EVs from MSC/Rluc cells (EV-MSC/Rluc) were visualized in a murine lung cancer model. The anticancer effects of EVs on Lewis lung carcinoma (LLC) and other cancer cells were assessed. EV-MSC/Rluc were visualized in vivo in the LLC-efffuc tumor model using optical imaging. The induction of apoptosis was confirmed with Annexin-V and propidium iodide staining. EV-MSC/Rluc and EV-MSCs showed a significant cytotoxic effect against LLC-effluc cells and 4T1; however, no significant effect on CT26, B16F10, TC1 cells. Moreover, EV-MSC/Rluc inhibited LLC tumor growth in vivo. EV-MSC/Rluc-mediated LLC tumor inhibitory mechanism revealed the decreased pERK and increased cleaved caspase 3 and cleaved PARP. We successfully developed luminescent EV-MSC/Rluc that have a therapeutic effect on LLC cells in both in vitro and in vivo. This bioluminescent EV system can be used to optimize EV-based therapy.
机译:间充质干细胞(MSC)可以用作癌症的治疗性装甲。已经评估了来自MSC的细胞外囊泡(EV)的抗癌作用。体内将电动汽车靶向肿瘤是成功治疗的基本要求。因此,在动物模型中监测电动汽车的非侵入性方法对于开发基于电动汽车的癌症疗法至关重要。本研究使用表达海肾荧光素酶(Rluc)的MSC开发生物发光电动汽车。在小鼠肺癌模型中可以看到来自MSC / Rluc细胞的EV(EV-MSC / Rluc)。评估了电动汽车对Lewis肺癌(LLC)和其他癌细胞的抗癌作用。 EV-MSC / Rluc使用光学成像在LLC-efffuc肿瘤模型中进行了体内观察。用膜联蛋白-V和碘化丙啶染色证实了细胞凋亡的诱导。 EV-MSC / Rluc和EV-MSC对LLC-effluc细胞和4T1具有明显的细胞毒性作用。但是,对CT26,B16F10,TC1细胞无明显影响。此外,EV-MSC / Rluc在体内抑制LLC肿瘤的生长。 EV-MSC / Rluc介导的LLC肿瘤抑制机制显示pERK减少,胱天蛋白酶3裂解和PARP裂解增加。我们成功开发了发光的EV-MSC / Rluc,可在体外和体内对LLC细胞产生治疗作用。这种生物发光电动汽车系统可用于优化基于电动汽车的疗法。

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