(P-CB-28) Synergistic Antileukemic Effects of Umbilical Cord Blood-Derived Exosomes and Cytarabine on U937 Acute Myeloid Leukemia Cells

Background/Case Studies:

Background: Acute myeloid leukemia (AML) is a type of blood cancer caused by abnormal proliferation of hematopoietic cells. While Cytarabine is a common medicine used to treat AML, new approaches are needed to improve outcomes. Recently, exosomes derived from umbilical cord blood mononuclear cells (CB-MNCs) and cord blood plasma (CBP) have emerged as promising therapeutic candidates due to their ability to modulate cellular signaling and induce apoptosis. This study aimed to evaluate the antileukemic effects of CB-MNCs and CBP-derived exosomes alone and in combination with Cytarabine on the U937 AML cell line.

Study

Design/Methods: Methods: Exosomes were isolated from human CBP and CB-MNCs and characterized by transmission electron microscopy, dynamic light scattering, and Western blotting. U937 cells were treated for 72 hours with CB-MNCs and CBP derived exosomes, Cytarabine, or their combination. Apoptosis was assessed by flow cytometry and caspase-3/7 activity assays. Quantitative real-time PCR evaluated expression of apoptosis-related genes. Western blotting analyzed NF-κB and AMPK signaling pathway activities.

Results/Findings:

Results: CB-MNCs-derived exosomes significantly induced apoptosis in U937 cells, though to a lesser extent than Cytarabine (19.6% vs. 44.1%, p < 0.05 and p < 0.0001, respectively). The combination treatment further enhanced apoptosis to 47.5% (p < 0.0001). Caspase-3/7 activity was elevated in both Cytarabine and combination groups (0.32 and 0.45 mU/mL, p < 0.001). Gene expression analysis demonstrated upregulation of pro-apoptotic and downregulation of anti-apoptotic genes, especially in the combination group. Both treatments inhibited NF-κB phosphorylation and activated AMPK signaling, with the combination showing the most pronounced effects. Furthermore, CBP-derived exosomes had minimal effects on the apoptosis rate.

Conclusions: CB-MNCs-derived exosomes exert antileukemic activity by promoting apoptosis and modulating NF-κB and AMPK pathways in U937 cells. the combination of Cord blood derived exosomes with Cytarabine causing synergistic effect, enhancing apoptotic induction and