Department of General Surgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Cancer Genomics Proteomics. 2021 Jul-Aug;18(4):569-578. doi: 10.21873/cgp.20281.
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.
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)-β (producing ASC-TRAIL and ASC-IFN-β, respectively). Death of H460 cells co-cultured with ASCs, ASC-TRAIL, and ASC-IFN-β 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-β-overexpressing ASCs was investigated.
Conditioned medium obtained from ASC-IFN-β 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-β both dramatically suppressed tumor growth. Interestingly, in the context of ASC-IFN-β, tumors were detected only in 20% of nude mice, with smaller sizes and lower weights than those of the control group.
TRAIL-overexpressing ASCs can be used to treat tumors; ASC-IFN-β in particular secrete a higher level of TRAIL.
背景/目的：间充质干细胞为基础的肿瘤治疗仍然受到限制，因为效应物的分泌不足，以及它们在体外和体内疗效之间的差异。我们研究了过表达肿瘤坏死因子相关凋亡诱导配体（TRAIL）的基因工程脂肪组织来源的间充质干细胞（ASCs）是否对 H460 肿瘤生长具有抑制作用，无论是在体外还是在 H460 异种移植模型中。
通过质粒转染 pCMV3-TRAIL 和 -干扰素（IFN）-β（分别产生 ASC-TRAIL 和 ASC-IFN-β）获得过表达肿瘤坏死因子相关凋亡诱导配体（TRAIL）的基因工程脂肪组织来源的间充质干细胞（ASCs）。通过凋亡和细胞毒性测定评估与 ASCs、ASC-TRAIL 和 ASC-IFN-β 共培养或暴露于其条件培养基的 H460 细胞的死亡情况。此外，在 H460 异种移植模型中（每组 n=10），研究了过表达 TRAIL 和 IFN-β 的 ASCs 的抗肿瘤潜力。
ASC-IFN-β 获得的条件培养基比 ASC-TRAIL 更能促进 H460 细胞的凋亡。此外，在 H460 异种移植模型中，虽然天然 ASCs 促进肿瘤生长，但 ASC-TRAIL 和 ASC-IFN-β 均能显著抑制肿瘤生长。有趣的是，在 ASC-IFN-β 的情况下，只有 20%的裸鼠检测到肿瘤，肿瘤体积较小，重量较对照组低。
过表达 TRAIL 的 ASCs 可用于治疗肿瘤；特别是 ASC-IFN-β 分泌更高水平的 TRAIL。
