Characterization of Urine Stem Cell-Derived Extracellular Vesicles Reveals B Cell Stimulating Cargo.

Asmaa A Zidan,Mohammed Al-Hawwas,Griffith B Perkins,Ghada M Mourad,Catherine J M Stapledon,Xin-Fu Zhou,Larisa Bobrovskaya,Plinio R Hurtado

doi:10.3390/ijms22010459

Abstract

Elucidation of the biological functions of extracellular vesicles (EVs) and their potential roles in physiological and pathological processes is an expanding field of research. In this study, we characterized USC–derived EVs and studied their capacity to modulate the human immune response in vitro. We found that the USC–derived EVs are a heterogeneous population, ranging in size from that of micro–vesicles (150 nm–1 μm) down to that of exosomes (60–150 nm). Regarding their immunomodulatory functions, we found that upon isolation, the EVs (60–150 nm) induced B cell proliferation and IgM antibody secretion. Analysis of the EV contents unexpectedly revealed the presence of BAFF, APRIL, IL–6, and CD40L, all known to play a central role in B cell stimulation, differentiation, and humoral immunity. In regard to their effect on T cell functions, they resembled the function of mesenchymal stem cell (MSC)–derived EVs previously described, suppressing T cell response to activation. The finding that USC–derived EVs transport a potent bioactive cargo opens the door to a novel therapeutic avenue for boosting B cell responses in immunodeficiency or cancer.

Highlights

Extracellular vesicles (EVs) were first described in human plasma by Peter Wolf as a form of platelet secretion and were known as platelet dust [1]
We report our findings on the characteristics of urine stem cells (USCs)–derived EVs at the ultrastructural level, as well as their immune–modulatory effects on human peripheral blood mononuclear cells (PBMCs)
We observed that the presence of EVs resulted in a significant increase in IL–6 (1600 ± 575 vs. 6476 ± 1160 pg/mL), interleukin 10 (IL–10) (7.5 ± 3.4 vs. 30.5 ± 7.9 pg/mL), TNFα (5.7 ± 1.3 vs. 38.6 ± 5.3 pg/mL), and soluble CD40L (40.7 ± 10.9 vs. 105.9 ± 10.4 pg/mL) concentration compared with

Summary

Introduction

Extracellular vesicles (EVs) were first described in human plasma by Peter Wolf as a form of platelet secretion and were known as platelet dust [1]. Subsequent studies showed that nano–and micro–sized membrane–bounded vesicles are constitutively secreted by a variety of cells, including mesenchymal stem cells (MSCs) [2,3]. These vesicles are generated in two main ways. EVs are lipid bilayer–bounded vesicles, which bear surface membrane proteins, and contain bioactive molecules such as microRNA, mRNA, cytokines, growth factors, and soluble proteins, and serve as messengers from the cell of origin [6]. Much attention has been directed at the immunomodulatory properties of MSC–derived vesicles, following the observation that MSCs exert anti–inflammatory and immuno–suppressive effects via direct cell-cell contact, as well as by cytokine and chemokine release, both in soluble form and loaded in EVs [10,11]

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