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

被引：57

作者：

Kalimuthu, Senthilkumar ^{[1
]}

Gangadaran, Prakash ^{[1
]}

Li, Xiu Juan ^{[1
]}

Oh, Ji Min ^{[1
]}

Lee, Ho Won ^{[1
]}

Jeong, Shin Young ^{[1
]}

Lee, Sang-Woo ^{[1
]}

Lee, Jaetae ^{[1
,2
]}

Ahn, Byeong-Cheol ^{[1
]}

机构：

[1] Kyungpook Natl Univ, Sch Med Hosp, Dept Nucl Med, Daegu 700721, South Korea

[2] Daegu Gyeongbuk Med Innovat Fdn, 80 Cheombok Ro, Daegu 701310, South Korea

来源：

SCIENTIFIC REPORTS | 2016年 / 6卷

基金：

新加坡国家研究基金会;

关键词：

BONE-MARROW; EXOSOMES; CANCER; GROWTH; MICROVESICLES; VISUALIZATION; BIODISTRIBUTION; MICROPARTICLES; PROLIFERATION; MICRORNAS;

D O I：

10.1038/srep30418

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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 (EVMSC/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.

引用

页数：11

共 65 条

[1] Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes [J].