The extracellular vesicles derived from TNF-α primed umbilical cord mesenchymal stromal cells enhance the maturation of natural killer cells through CCL2/CCR2 pathway

Le résumé fourni par la source

Cytokine priming is a common strategy to enhance the immunostimulatory properties of mesenchymal stromal cells (MSCs). Extracellular vesicles (MSC-EVs) secreted from primed MSCs can restore immune function in clinical settings. Natural killer cells (NK cells) are among the target cells involved in cancer elimination. NK cell dysfunction is frequently observed in patients with severe cancer, and recombinant cytokine therapy has been unable to revive their function. This research emphasizes the importance of primed MSCs in enhancing the potential of EVs for immune boosting. Peripheral blood mononuclear cells (PBMCs) and NK cells were treated with Con-EV and TNF-EV to identify the NK cells. NK cell populations were determined using surface markers by flow cytometry. The immune mediator proteins of TNF-EV and Con-EV were measured. The CCL2/CCR2 pathway signaling proteins in NK cells were explored for the effects of TNF-EV and Con-EV using western blot. TNF-α enhanced MSC-EVs secretion. PBMC and NK cell proliferation were significantly increased by TNF-EV, while Con-EV suppressed. CCL2 expression in TNF-EV was significantly higher compared to Con-EV. TNF-EV increased NF-κB expression in NK cells through the CCL2/CCR2 pathway, and the CCR2 inhibitor reverses the effects of TNF-EV on NK cell proliferation and maturation. TNF-EV induced PBMC and NK cell maturation. TNF-EV contained high concentration of CCL2, activating CCL2/CCR2 pathways on NK cells and promoting NK cell maturation. TNF-EV could be used for ex vivo expansion of NK cells as a xeno-free supplement. Further animal model studies are required to support the anti-tumor effect of TNF-EV and to develop it as an alternative cell-free therapy to boost NK cell activity in patients.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.