TRAIL-overexpressing Adipose Tissue-derived Mesenchymal Stem Cells Efficiently Inhibit Tumor Growth in an H460 Xenograft Model

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)-beta (producing ASC-TRAIL and ASC-IFN-beta, respectively). Death of H460 cells co-cultured with ASCs, ASC-TRAIL, and ASC-IFN-beta 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-beta-overexpressing ASCs was investigated. Results: Conditioned medium obtained from ASC-IFN-beta increased apoptosis of H460 cells more than did ASC-TRAIL. Additionally, in H460 xenograft models, while native ASCs promoted tumor growth, ASC-TRAIL and ASC-IFN-beta both dramatically suppressed tumor growth. Interestingly, in the context of ASC-IFN-beta, 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-beta in particular secrete a higher level of TRAIL.