Pretreatment of umbilical cord derived MSCs with IFN-γ and TNF-α enhances the tumor-suppressive effect on acute myeloid leukemia

In the current study, we found that umbilical cord-derived mesenchymal stem cells (UC-MSCs) efficiently induce acute myeloid leukemia (AML) cell apoptosis by inducing tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) and indoleamine 2,3-dioxygenase (IDO) expression. IFN-γ and TNF-α produced by AML cells augment the expression of TRAIL and IDO. Pretreating UC-MSCs with IFN-γ and TNF-α can enhance the anti-leukemia effect activity of UC-MSCs in vitro and in vivo. Our findings provided a novel and safe stem cell-based therapeutic strategy for potential application in AML treatment. [Display omitted] Currently, the standard therapeutic approach of AML consists of chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT). However, these strategies are usually associated with adverse side effects and high risk of relapse following HSCT. Thus, it is imperative to find an alternative way against AML progression. Here, we showed that treatment with umbilical cord-derived mesenchymal stem cells (UC-MSCs) could efficiently induce apoptosis in both primary AML patient-derived leukemic cells and AML cell lines. Mechanistically, tumor necrosis factor-α-related apoptosis-inducing ligand (TRAIL) in UC-MSCs mediated the proapoptotic effect in AML cells. Besides, indoleamine 2,3-dioxygenase (IDO) secreted by UC-MSCs blocked the cell cycle progression and inhibited the proliferation of AML cells. Importantly, we found that incubation of UC-MSCs with IFN-γ and TNF-α could upregulate the expression of TRAIL and IDO, resulting in an intensive pro-apoptotic efficacy. UC-MSCs pre-treatment could not only relieve the AML burden but also eliminate AML cells in a xenograft AML model. Our findings have shed light on an effective pre-activated approach to aggravating the anti-leukemia effect of MSC. Furthermore, a novel and safe stem cell-based therapy approach for AML treatment.