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- Title
TRAIL-overexpressing Adipose Tissue-derived Mesenchymal Stem Cells Efficiently Inhibit Tumor Growth in an H460 Xenograft Model.
- Authors
YOUNG UN CHOI; YONGDAE YOON; PIL YOUNG JUNG; SOONJAE HWANG; JU EUN HONG; WOO-SEUNG KIM; JOON HYUNG SOHN; KI-JONG RHEE; KEUM SEOK BAE; YOUNG WOO EOM
- Abstract
Background/Aim: Mesenchymal stem cell-based tumor therapy is still limited due to the insufficient secretion of effectors and discrepancies between their in vitro and in vivo efficacy. We investigated whether genetically engineered adipose tissue-derived mesenchymal stem cells (ASCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) had inhibitory effects on H460 tumor growth both in vitro and in an H460 xenograft model. Materials and Methods: Genetically engineered adipose tissue-derived mesenchymal stem cells (ASCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were obtained from plasmid transfection with pCMV3-TRAIL and -interferon (IFN)-ß (producing ASC-TRAIL and ASC-IFN-ß, respectively). Death of H460 cells co-cultured with ASCs, ASC-TRAIL, and ASC-IFN-ß or exposed to their conditioned medium was evaluated via apoptosis and cytotoxicity assays. In addition, in an H460 xenograft model (n=10 per group), the antitumor potential of TRAIL-overexpressing, and IFN-ß-overexpressing ASCs was investigated. Results: Conditioned medium obtained from ASCIFN-ß increased apoptosis of H460 cells more than did ASCTRAIL. Additionally, in H460 xenograft models, while native ASCs promoted tumor growth, ASC-TRAIL and ASC-IFN-ß both dramatically suppressed tumor growth. Interestingly, in the context of ASC-IFN-ß, tumors were detected only in 20% of nude mice, with smaller sizes and lower weights than those of the control group. Conclusion: TRAIL-overexpressing ASCs can be used to treat tumors; ASC-IFN-ß in particular secrete a higher level of TRAIL.
- Subjects
MESENCHYMAL stem cells; TUMOR growth; CELL death; NECROSIS
- Publication
Cancer Genomics & Proteomics (1109-6535), 2021, Vol 18, Issue 4, p569
- ISSN
1109-6535
- Publication type
Article
- DOI
10.21873/cgp.20281