Human umbilical cord mesenchymal stem cells derived extracellular vesicles regulate acquired immune response of lupus mouse in vitro

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. Immunopathology believes that abnormal T cell function and excessive production of autoantibodies by B cells are involved in multi-organ damage. Human umbilical cord mesenchymal stem cells (hUCMSCs) therapies have endowed with promise in SLE, while the function of MSC-derived extracellular vesicles (MSC-EVs) was still unclear. Extracellular vesicles (EVs) are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles. EVs play a vital role in cell-to-cell communication by acting as biological transporters. New evidence has shown beneficial effects of MSC-EVs on autoimmune diseases, such as their immunomodulatory properties. In this study, we investigated whether hUCMSCs derived extracellular vesicles (hUCMSC-EVs) could regulate abnormal immune responses of T cells or B cells in SLE. We isolated splenic mononuclear cells from MRL/lpr mice, a classical animal model of SLE. PBS (Phosphate-buffered saline), 2 × 105 hUCMSCs, 25 µg/ml hUCMSC-EVs, 50 µg/ml hUCMSC-EVs were co-cultured with 2 × 106 activated splenic mononuclear cells for 3 days in vitro, respectively. The proportions of CD4+ T cell subsets, B cells and the concentrations of cytokines were detected. Both hUCMSCs and hUCMSC-EVs inhibited CD4+ T cells, increased the production of T helper (Th)17 cells, promoted the production of interleukin (IL)-17 and transforming growth factor beta1 (TGF-β1) (P < 0.05), although they had no significant effects on Th1, Th2, T follicular helper (Tfh), regulatory T (Treg) cells and IL-10 (P > 0.05); only hUCMSCs inhibited CD19+ B cells, promoted the production of interferon-gamma (IFN-γ) and IL-4 (P < 0.05). hUCMSCs exert immunoregulatory effects on SLE at least partially through hUCMSC-EVs in vitro, therefore, hUCMSC-EVs play novel and potential regulator roles in SLE.

Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE

“…They have shown that UC-MSCs exert immunoregulatory effects on SLE, partially mediated by their EVs. UC-MSC-EVs were able to inhibit CD4+ T cells in their model, but lower amounts of TGF-β and IL-17 were found in the supernatant ( 201 ). Another study also using UC-MSC-EVs has shown an amelioration of SLE after EV administration in MRL/lpr mice by inducing M2 macrophages polarization and increasing regulatory T cell ( 202 ).…”

The relationship between kidney disease and mitochondria: a bibliometric study

“…ROS) through the mitochondrial electron transport chain [ 6 ]. In addition, there are not many related keywords for emerging research directions in recent years, such as mitochondrial DNA (mtDNA) leakage [ 7–9 ], mitochondrial dynamics [ 10 , 11 ], and the role of mitochondria in immunity [ 12 , 13 ]. This reminds us that mitochondria, as organelles, have been noticed by researchers, and the focus has gradually shifted from functional abnormalities to mechanisms and gradually refined in content.…”

Human Umbilical Cord Mesenchymal Stem Cells Repair Endothelial Injury and Dysfunction by Regulating NLRP3 to Inhibit Endothelial Cell Pyroptosis in Kawasaki Disease

“…MSCs can not only differentiate into various types of cells but also have unique immunomodulatory properties through paracrine signaling or the release of extracellular vesicles, which provides new opportunities for the treatment of autoimmune diseases, such as RA, SLE and in ammatory bowel disease (IBD) [32][33][34][35][36]42]. However, autoimmune diseases do not have a precise pathogenesis, and several studies have reported that the NLRP3 in ammasome is associated with susceptibility, disease severity and treatment effects [43][44][45].…”

“…Due to their biological characteristics of low immunogenicity and immune regulation, Huc-MSCs have been widely studied and applied in many autoimmune diseases, such as SLE [32][33][34] and RA [35,36]. However, there have been few reports on the treatment of KD vasculitis with Huc-MSCs.…”