Human Adipose Tissue-Derived Mesenchymal Stem Cells Inhibit the Growth of Murine T-Cell Lymphoma in vitro and in vivo

Abstract

The prognosis of patients with T-cell lymphoma is guarded to poor, and new treatments are needed. Emerging evidence has suggested that human mesenchymal stem cells (MSCs) play an important role in the development and growth of human malignancy. This study investigated the anti-tumor effect of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) in T-cell lymphoma in vitro and in vivo. Co-culture of T-cell lymphoma cells with hAT-MSCs inhibited EL4 cell growth on day 3. Flow cytometry demonstrated the G0/G1 phase accumulation in EL4 cells treated with hAT-MSCs, and Annexin V/propidium iodide staining showed that hAT-MSCs induced EL4 cell apoptosis. When apoptotic effects induced by hAT-MSCs in tumor cells were observed by Western blot assay, hAT-MSCs modulated the expression of apoptosis-related proteins, caspase-3, and poly ADP-ribose polymerase in EL4 cells. Expression of tumor necrosis factor-related apoptosis-inducing ligand mRNA was up-regulated three-fold in hAT-MSCs co-cultured with EL4 cells, but Dickkorf-related protein-1 mRNA expression was not affected, as evaluated by the reverse transcription-polymerase chain reaction. The results of fluorescence microscope analysis showed that hAT-MSCs labeled with CM-Di1 migrated into tumors of EL4 T-cell lymphoma mice. Tumor volume and body weights in the hAT-MSCs treated group were smaller than those in the control group. Additionally, life span was prolonged in the hAT-MSCs treated group. In conclusion, these results demonstrate that hAT-MSCs suppress the growth of T-cell lymphoma by altering cell cycle progression and inducing apoptosis in vitro and in vivo, suggesting a therapeutic option for T-cell lymphoma.