Mesenchymal Stromal Stem Cell-Derived Microvesicles Enhance Tumor Lysate Pulsed Dendritic Cell Stimulated Autologous T lymphocyte Cytotoxicity

Document Type: Research Articles

Authors

1 Department of Clinical Biochemistry, Ardabil University of Medical Sciences, Ardabil, Iran.

2 Department of Microbiology, Division of Immunology, Veterinary Faculty, Urmia University, Urmia, Iran.

Abstract

Background: Immunotherapy is one promising therapeutic strategy against glioma, an aggressive form of brain
cancer. Previous studies have demonstrated that multiple tumor antigens exist and can be used to induce tumor specific
T cell responses. Furthermore, recently it was shown that TLR4-primed mesenchymal stem cells (MSCs), also known
as MSC1, mostly elaborate pro-inflammatory mediators. Compared to MSCs, MSC-derived microvesicles (MVs) have
advantageous properties that present them as stable, long lasting effectors with no risk of immune rejection. Therefore,
peripheral blood monocyte derived dendritic cells (MoDCs) have been used to load tumor antigens and stimulate T
cell mediated responses in the presence of MSC1-derived MVs in vitro. Methods: The B92 tumor cell line was heated
to 43°C for 90 min prior to preparation of tumor cell lysates. MVs were purified by differential ultracentrifugation
after isolation, stimulation of proliferation and treatment of MSCs. Autologous T cells isolated from non-adherent
cells were harvested during the procedure to generate MoDCs and then incubated with heat stressed tumor cell lysate
pulsed DCs in the presence of MSC1-derived MVs. T cells were then co-cultured with tumor cells in 96-well plates at
a final volume of 200 μl CM at an effector: target ratio of 100:1 to determine their specific cytotoxic activity. Results:
Flow cytometric analysis, T cell mediated cytotoxicity showed that heat stressed tumor antigen pulsed MoDCs and
MSC1-derived MVs primed T cells elicited non-significantly enhanced cytotoxic activity toward B92 tumor cells
(P≥0.05). Conclusion: These findings may offer new insights into tumor antigen presenting technology involving
dendritic cells and MSC1-derived MVs. Further exploration of the potential of such nanoscale particles in immunotherapy
and in novel cancer vaccine settings appears warranted.

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