Yüce Melek, Albayrak Esra
Stem Cell Research & Application Center, Ondokuz Mayıs University, Kurupelit Campus, Atakum/Samsun, Turkey.
J Cell Biochem. 2022 Dec;123(12):1966-1979. doi: 10.1002/jcb.30322. Epub 2022 Aug 27.
There are contradictory reports on the use of mesenchymal stromal cells (MSCs) in cancer therapy. Variable outcomes have been associated with several factors including cancer pathology, experimental procedure, MSC source tissue, and individual genetic differences. It is also known that MSCs exert their therapeutic effects with various paracrine factors released from these cells. The profiles of the factors released from MSCs are altered by heat shock, hypoxia, oxidative stress, starvation or various agents such as inflammatory cytokines, and their therapeutic potential is affected. In this study, the antitumor potential of conditioned media (CM), which contains paracrine factors, of mild hyperthermia-stimulated mesenchymal stromal cells derived from lymphoid organ tonsil tissue (T-MSC) was investigated in comparison with CM obtained from T-MSCs grew under normal culture conditions. CM was obtained from T-MSCs that were successfully isolated from palatine tonsil tissue and characterized. The cytotoxic effect of CM on the growth of hematological cancer cell lines at different concentrations (1:1 and 1:2) was demonstrated by methylthiazoldiphenyl-tetrazolium bromide analysis. In addition, the apoptotic effect of T-MSC-CM treatment was evaluated on the cancer cells using Annexin-V/PI detection method by flow cytometry. The pro/anti-apoptotic and cytokine-related gene expressions were also analyzed by real-time polymerase chain reaction post T-MSC-CM treatment. In conclusion, we demonstrated that the factors released from hyperthermia-stimulated T-MSCs induced apoptosis in hematological cancer cell lines in a dose-dependent manner. Importantly, our results at the transcriptional level support that the factors and cytokines released from hyperthermia-stimulated T-MSC may exert antitumoral effects in cancer cells by downregulation of IL-6 that promotes tumorigenesis. These findings reveal that T-MSC-CM can be a powerful cell-free therapeutical strategy for cancer therapy.
关于间充质基质细胞（MSCs）在癌症治疗中的应用，存在相互矛盾的报道。多种因素与不同的结果相关，包括癌症病理学、实验程序、MSCs来源组织以及个体遗传差异。还已知MSCs通过这些细胞释放的各种旁分泌因子发挥其治疗作用。MSCs释放的因子谱会因热休克、缺氧、氧化应激、饥饿或各种试剂（如炎性细胞因子）而改变，其治疗潜力也会受到影响。在本研究中，与从正常培养条件下生长的扁桃体来源的间充质基质细胞（T-MSCs）获得的条件培养基（CM）相比，研究了轻度热刺激的源自淋巴器官扁桃体组织的间充质基质细胞（T-MSCs）的CM的抗肿瘤潜力。CM是从成功从腭扁桃体组织分离并鉴定的T-MSCs中获得的。通过甲基噻唑二苯基四氮唑溴盐分析证明了不同浓度（1:1和1:2）的CM对血液癌细胞系生长的细胞毒性作用。此外，使用膜联蛋白-V/碘化丙啶检测方法通过流式细胞术评估了T-MSC-CM处理对癌细胞的凋亡作用。在T-MSC-CM处理后，还通过实时聚合酶链反应分析了促凋亡/抗凋亡和细胞因子相关基因的表达。总之，我们证明了热刺激的T-MSCs释放的因子以剂量依赖性方式诱导血液癌细胞系凋亡。重要的是，我们在转录水平的结果支持，热刺激的T-MSC释放的因子和细胞因子可能通过下调促进肿瘤发生的IL-6在癌细胞中发挥抗肿瘤作用。这些发现表明，T-MSC-CM可以成为一种强大的无细胞癌症治疗策略。
