title: In Vivo therapeutic potential of mesenchymal stem cell-derived extracellular vesicles with optical imaging reporter in tumor mice model.
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.
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Kalimuthu
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Prakash
authors.initials: P
authors.lastname: Gangadaran
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Xiu Juan
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Oh
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Ho Won
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Shin Young
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Sang-Woo
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.|Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu 701-310, Republic of Korea.
authors.forename: Jaetae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Kyungpook National University School of Medicine/Hospital, Daegu 700-721, Republic of Korea.
authors.forename: Byeong-Cheol
authors.initials: BC
authors.lastname: Ahn
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D045744:Cell Line, Tumor; D002470:Cell Survival; D004195:Disease Models, Animal; D000067128:Extracellular Vesicles / Q000378:metabolism*; D015870:Gene Expression; D017930:Genes, Reporter; D008163:Luminescent Measurements / Q000379:methods; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D057054:Molecular Imaging; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D014161:Transduction, Genetic
chemical_list: D015415:Biomarkers