Human Umbilical Cord Mesenchymal Stem Cell-Derived Microvesicles Could Induce Apoptosis and Autophagy in Acute Myeloid Leukemia

Authors
Mohammad Khani-Eshratabadi 1
Seyed Hadi Mousavi 1
Morteza Zarrabi 2
Jamal Motallebzadeh Khanmiri 1
Zahra Zeinali Bardar 3
1 Department of Hematology and Blood Transfusion Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
3 Kashmar School of Medical Sciences, Mashhad University of Medical Sciences, Mashhad, Iran
10.61186/ibj.27.5.247
Abstract
Background: Microvesicles (MV) have been identified as candidate biomarkers for treating acute myeloid leukemia (AML). This study investigated the effects of human umbilical cord-derived mesenchymal stem cell (hUCMSC)-derived MVs on apoptosis and autophagy in the KG-1 leukemic cell line.

Methods: The hUCMSCs were cultured and characterized by flow cytometry. MVs were isolated by ultracentrifugation, and the concentration was determined using the Bradford method. The characteristics of MVs were confirmed by transmission electron microscopy, flow cytometry, and dynamic light scattering methods. KG-1 cells were treated with the desired concentrations of MVs for 24 h. The apoptosis induction and reactive oxygen species production were evaluated using flow cytometry. RT-PCR was performed to evaluate apoptosis- and autophagy-related genes expression.

Results: Following tretment of KG-1 cells with 25, 50, and 100 μg/ml concentrations of MVs, the apoptosis rates were 47.85%, 47.15%, and 51.35% (p < 0.0001), and the autophagy-induced ROS levels were 73.9% (p < 0.0002), 84.8% (p < 0.0001), and 85.4% (p < 0.000), respectively. BAX and ATG7 gene expression increased significantly at all concentrations compared to the control, and this level was higher at 50 μg/ml than that of the other concentrations. In addition, LC3 and Beclin 1 expression increased significantly in a concentration-dependen manner. Conversely, BCL2 expression decreased compared to the control.

Conclusion: Our findings indicate that hUCMSC-MVs could induce cell death pathways of autophagy and apoptosis in the KG-1 cell lines and exert potent antiproliferative and proapoptotic effects on KG-1 cells in vitro. Therefore, hUCMSC-MVs may be a potential approach for cancer therapy as a novel cell-to-cell communication strategy.
Keywords
Acute myeloblastic leukemia
Apoptosis
autophagy
Mesenchymal stem cells