Induction of Cell Death in U937 Myeloid Leukemia Cell Line Co-cultured with Genetically Engineered Adipose-derived Stem Cells Expressing a High Level of Bone Morphogenetic Protein 4 through miR-424-5p

Acute myeloid leukemia (AML) is a heterogeneous and complex malignancy characterized by rapid cellular proliferation, an aggressive clinical course, and generally high mortality. Transforming growth factor-beta (TGF-β) plays a significant role in tumorigenesis. Bone morphogenetic protein 4 (BMP4) is a member of the TGF-β superfamily whose expression is mainly controlled by the Smad signaling pathway. Studies have shown that this protein can control and induce the expression of some microRNAs during the cancer treatment process. MiR-424-5p plays an essential role in various types of cancer at different stages of tumorigenesis, including the promotion and/or inhibition of tumorigenesis, regulation of tumor development in the tumor microenvironment, and influencing cancer chemotherapy outcomes. The aim of this study was to evaluate the induction of cell death in the U937 myeloid leukemia cell line co-cultured with genetically engineered adipose-derived stem cells (ADSCs) expressing a high level of BMP4 through miR-424-5p. The induction of cell death and apoptosis in the U937 cell line was assessed using MTT and Annexin V/ PI assays, respectively. The expression of miR-424 and TGF-β was determined in the co-culture system using real-time PCR. The results of MTT and Annexin V/ PI assays showed that BMP4-expressing adipose-derived stem cells (ADSCs) induced cell death in U937 cells in the co-culture system. Co-culture of engineered ADSCs with the U937 cell line led to the downregulation of miR-424 and TGF-β genes in U937 cells. In the current study, a new strategy based on BMP4 induction was designed to significantly suppress the cell viability of the leukemia cell line U937. It appears that the use of engineered ADSCs could be useful for the treatment of hematological malignancies.