Therapeutic potential of exosomes derived from mesenchymal stem cells for treatment of systemic lupus erythematosus

Abstract

Autoimmune diseases are caused by an imbalance in the immune system, producing autoantibodies that cause inflammation leading to tissue damage and organ dysfunction. Systemic Lupus Erythematosus (SLE) is one of the most common autoimmune diseases and a major contributor to patient morbidity and mortality. Although many drugs manage the disease, curative therapy remains elusive, and current treatment regimens have substantial side effects. Recently, the therapeutic potential of exosomes has been extensively studied, and novel evidence has been demonstrated. A direct relationship between exosome contents and their ability to regulate the immune system, inflammation, and angiogenesis. The unique properties of extracellular vesicles, such as biomolecule transportation, biodegradability, and stability, make exosomes a promising treatment candidate for autoimmune diseases, particularly SLE. This review summarizes the structural features of exosomes, the isolation/purification/quantification method, their origin, effect, immune regulation, a critical consideration for selecting an appropriate source, and their therapeutic mechanisms in SLE.

Fig. 1

EV biogenesis, cargo contents, and uptake. HSP, heat shock proteins; SCAMPs, secretory carrier membrane proteins; Alix, Apoptosis-linked gene 2–interacting protein X; HRS, hepatocyte growth factor-regulated tyrosine kinase substrate; TSG101, tumor susceptibility gene 101

Fig. 2

The development of systemic lupus erythematosus (SLE) and lupus nephritis (LN). The schematic diagram illustrates how hyperactivated immune cells cause disease progression, and serum and urinary EV components and miRNAs level could be regarded as disease initiation and progression markers. genetic and epigenetic factors trigger SLE formation. during disease progression, DNAs and apoptotic cells stimulate the activity of B cells by stimulating peripheral blood mononuclear cells (PBMCs) to produce TNF-α, IL-1β, and IL-6, which causes T cell necrosis and autoantibodies production. Moreover, T cell stimulates cytokine production (TNF-α, IL-1β, IL-8, IL- 12, and IL-6) through antigen-presenting cells (APCs) and B cell activation. microparticles (MPs) also increase IL-6, TNF-α, INF-α, and ultimately, autoantibodies production and tissue injury. High reactive oxygen species (ROS) production and reduced glutathione (GSH) also evaluated T cell necrosis and increased cardiovascular disease risk. In plasma exosomes, miRNAs (miR-574, let-7b, and miR-21) expression increases IFN-α production through TLR7 signaling via stimulating plasmacytoid DCs (pDCs). urinary exosomes, including miR-26a, miR-21, miR-29 C, miR-135b-5p, miR-107, miR-31, miR-146a, miR-150 promote renal fibrosis are candidate biomarkers for LN and SLE. additionally, cerulo plasmin (CP), a protein from urinary exosomes, could be regarded as an early biomarker to diagnose kidney disease