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A: 간엽줄기세포로부터 EV가 성공적으로 분리되었음을 증명함. B: Rluc가 이입된 간엽줄기세포에서 분리된 EV에서는 Rluc이 발현되며, 영상신호를 발생함을 보여줌. C, D: 간엽줄기세포 유래 EV가 세포배양실험 및 동물실험에서 폐암세포의 증식을 억제함을 증명함.​

Abstract

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. 

Author information​

Kalimuthu S1, Gangadaran P1, Li XJ1, Oh JM1, Lee HW1, Jeong SY1, Lee SW1, Lee J1,2, Ahn BC1.

1Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.

2Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu 701-310, Republic of Korea.