Potent improvement in the immunomodulatory effects of mesenchymal stromal/stem cells following treatment with Mesobuthus eupeus whole venom and F1 fraction.

INTRODUCTION

This study was evaluated the impact of Mesobuthus eupeus (M. eupeus) whole venom and its derived fractions on the expression levels of immunomodulatory and functional factors of mesenchymal stem cells (MSC) and their capacity to induce regulatory T cells (Treg) through small extracellular vesicle (sEV) mechanisms.

MATERIALS AND

METHODS

Human umbilical cord-derived MSCs (UC-MSC) from a single healthy full-term mother were treated over a 24-h period with 100 μg/mL of whole venom (WV), F1, F2, F3, and F4 fractions, separately (in triplicate). Then, the expression of Galectin1, Galectin 3, Galectin 8, TLR2, TLR4, IL-10, TGF-β, HGF, IDO, SOX2, and OCT4 were evaluated through SYBR Green real-time polymerase chain reaction (PCR). Next, peripheral blood mononuclear cells (PBMC) were isolated from five healthy subjects and treated 24 h by sEVs derived from venom- and fraction-treated MSCs (in triplicate) and the percentage of regulatory T cells (Treg) were assessed through flow cytometry.

RESULTS

WV and F1 have significant effects on the gene expressions and sEV-treated Treg induction, while no significant changes were observed following F2, F3, and F4 treatments.

CONCLUSION

WV and F1 fraction could potentially administer as a pre-treatment agent to improve the immunomodulatory and immune-regulatory effects of MSCs.