Microvesicles Derived from Human Placental Mesenchymal Stem Cells Induce Autophagy and Apoptosis in Acute Myeloid Leukemia

 Acute myeloid leukemia (AML) has a complex course of treatment, including chemotherapy and bone marrow transplantation, which mostly results in drug resistance and recurrence. Therefore, alternative therapies have attracted the attention of researchers. Mesenchymal stem cells exert their paracrine effects through the secretion of multiple cytokines and vesicles. Recent findings suggest the possible antitumor properties of MSCs by the secretion of micro-vesicles, and consequent activation of cell death pathways in cancer cells. The present study evaluated how micro-vesicles from human placental mesenchymal stem cells affect the autophagy and apoptosis pathways in AML.

 After isolation and culture, hPMSCs were identified through flow cytometry. The Bradford method was employed to determine the concentration of MVs. The properties of MVs were confirmed by transmission electron microscopy (TEM) and DLS. Next, the KG1 cell line was exposed to MVs at concentrations of 25, 50, and 100 μg/ml for 24 hours. Subsequently, apoptosis was assessed using an Annexin V-FITC/PI kit, and ROS activity was gauged through the utilization of H2DCFDA. The gene expression in the autophagy and apoptosis pathways was investigated by using the real-time PCR technique.

 After 24 hours of treatment, a rise in intracellular ROS accumulation and apoptosis was observed in all groups compared to the control group. The mean intracellular ROS accumulation at the concentrations of 25, 50, and 100 μg / ml of the samples and the control group was 62.21% (P<0.0002), 66.25% (P<0.0001), 62.55% (P<0.0001), and 26.1% (P<0.0001), respectively. The apoptosis indices at the concentrations of 25, 50, and 100 μg / ml of the samples were 62.6% (P<0.0002), 46.0% (P<0.0001), and 48.2% (P<0.0001), respectively. Furthermore, analyzing genes through RT-PCR indicated a considerable increase in the expression of autophagy-related and pro-apoptotic genes.

 Our findings indicate that hPMSC-MVs induce Cell death pathways of autophagy and apoptosis in the KG1 cell lines. Additionally, hPMSC-MVs exhibited heightened impactful anti-proliferative and pro-apoptotic outcomes on KG1 cells in vitro.