Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Human Adipose Stem Cell-derived Extracellular Vesicles Induce Immune Responses in Mice but Not in Human Peripheral Blood Mononuclear Cells

Version 1 : Received: 1 December 2022 / Approved: 5 December 2022 / Online: 5 December 2022 (09:01:51 CET)

How to cite: Kim, D.O.; Choi, Y.C.; Kim, W.; Choi, J.S.; Lee, K.S.; Cho, Y.W.; Lee, B.; Yoo, M.H. Human Adipose Stem Cell-derived Extracellular Vesicles Induce Immune Responses in Mice but Not in Human Peripheral Blood Mononuclear Cells. Preprints 2022, 2022120069. https://doi.org/10.20944/preprints202212.0069.v1 Kim, D.O.; Choi, Y.C.; Kim, W.; Choi, J.S.; Lee, K.S.; Cho, Y.W.; Lee, B.; Yoo, M.H. Human Adipose Stem Cell-derived Extracellular Vesicles Induce Immune Responses in Mice but Not in Human Peripheral Blood Mononuclear Cells. Preprints 2022, 2022120069. https://doi.org/10.20944/preprints202212.0069.v1

Abstract

Human adipose stem cell-derived extracellular vesicles (hASC-EVs) are key mediators of paracrine signaling with promising therapeutic applications. Although hASC-EVs are derived from human cells and are less immunogenic, their immunogenicity cannot be completely excluded. Here, we evaluate the immune responses of ICR and C57BL/6 mice to high doses of hASC-EVs for 10 days after injection. Lymphocyte subpopulations are analyzed using flow cytometry at 0.5, 1, 3 and 24 h post injection. In the spleen and blood of C57BL/6 mice, neutrophils sharply increased at 0.5 h and decreased at 3 h following hASC-EV treatment. We observe increased proportions of monocytes, macrophages, and natural killer cells at 3 h but returned to similar level of vehicle control at 24 h post injection in the spleen and blood of ICR mice. Although the in vivo experiments reveal different immune responses to hASC-EV treatment in C57BL/6 and ICR strains, no major changes occur in human peripheral blood mononuclear cell composition after applying hASC-EVs in vitro. In conclusion, unlike those in mice, immune responses to hASC-EVs in humans are not detectable, indicating a minimal risk of fatal side-effects from hASC-EV-based therapies.

Keywords

human adipose mesenchymal stem cell; human peripheral blood mononuclear cells; cytokine; immune cell frequency; C57BL/6 mouse; ICR mouse

Subject

Medicine and Pharmacology, Immunology and Allergy

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