Hyperthermia‐stimulated tonsil‐mesenchymal stromal cells suppress hematological cancer cells through downregulation of IL‐6

Abstract

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.

Impact of Low-Temperature Plasma Radiofrequency Tonsillectomy on Pain, Inflammatory Markers, and Sleep Quality in Adults with Chronic Tonsillitis

“…IL-6 is a mul-tifunctional cytokine associated with inflammation, infection, and tissue damage. In CT, repeated stimulation of the immune system by bacteria and viruses can lead to an elevation in IL-6 levels [26]. Although an increase in IL-6 is a physiological response to inflammation, prolonged elevation may lead to an overactive immune system, exacerbating inflammation [27].…”

Conditioned media of tonsil derived mesenchymal stem cells shows different rates of cytotoxicity on solid cancer cells

“…Human tonsil derived mesenchymal stem cell isolation Tonsil tissues were obtained from donors who underwent tonsillectomy with the approval of the donor and the clinical research ethics committee. TMSCs were enzymatically isolated and characterized as described in our previous study, 17 and cultured with DMEM supplemented with 10% Fetal Bovine Serum (FBS, Gibco), and 1% antibioticantimycotic (Sigma Aldrich). Characterization was done in the second or third passages.…”

“…The adipogenic and osteogenic differentiation protocol was performed as in our previous study. 17 Briefly, the 10×10⁴ cells were cultured in the six well plate with the specific differentiation mediums for 3 weeks. The differentiation mediums were changed every two days.…”

“…The absorbance data were analyzed using Prism 7.00 (GraphPad Software, Inc) program compared to untreated control cells. 17 All experiments were performed in triplicate.…”

“…16 In the studies of the authors investigating the effect of TMSC-CM on hematological cancer cell lines, it was shown that CM induces cell death in hematological cancers after heat induction of TMSCs. 17 It causes changes in cancer behavior depending on the variability of the tumor niche in hematological and solid cancers. 18 Studies have supported that different therapeutic responses to the same therapeutic agent occur in hematological and solid cancers.…”