Molecular and therapeutic effects of mesenchymal stem cell-derived exosomes on autoimmune diseases

Abstract

Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms. Conventional treatment strategies, such as immunosuppressive drugs and anti-inflammatory therapies, often demonstrate limited efficacy and are associated with considerable side effects. Recently, mesenchymal stem cells (MSCs) have attracted growing interest as a promising therapeutic approach, owing to their immunomodulatory properties and ability to promote tissue repair. However, the direct application of MSCs faces several limitations, including the risk of immunogenicity and difficulties in large-scale production. In this context MSC-derived exosomes (MSC-Exos), nano-sized extracellular vesicles secreted by MSCs, have emerged as a compelling alternative to cell-based therapies. Enriched with proteins, lipids, and nucleic acids, these exosomes exhibit potent anti-inflammatory and immunomodulatory effects. Their primary mechanisms of action include enhancing the population of regulatory T cells, modulating macrophage polarization, and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. The therapeutic potential of MSC-Exos extends beyond individual conditions, encompassing a wide range of autoimmune diseases. For instance in Behçet's disease, they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration. Moreover, MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. Through mechanisms such as inflammation suppression, vascular repair, and the restoration of immune homeostasis, MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy. This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases, with particular emphasis on their clinical potential in Behçet's disease, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.

Keywords: Autoimmune diseases; Behçet’s disease; Exosomes; Immunomodulation; Mesenchymal stem cells; Multiple sclerosis; Rheumatoid arthritis; Systemic lupus erythematosus.

Figure 1

Biogenesis and composition of exosomes. Created with BioRender.com. miRNA: MicroRNA.

Figure 2

Immunopathogenesis of Behçet’s disease and potential therapeutic effects of mesenchymal stem cells/mesenchymal stem cell-derived exosomes. Created with BioRender.com. MSCs: Mesenchymal stem cells; MSC-Exos: Mesenchymal stem cell-derived exosomes; MHC-II: Major histocompatibility complex class II; TCR: T cell receptor; IFN-γ: Interferon-gamma; TNF-α: Tumor necrosis factor-alpha; IL-12: Interleukin-12; Treg: Regulatory T cell; Th1: T helper 1; Th17: T helper 17; TGF-β: Transforming growth factor-beta; GM-CSF: Granulocyte-macrophage colony-stimulating factor; M-CSF: Macrophage colony-stimulating factor; γδ T cells: Gamma delta T cells; M1: Proinflammatory macrophage; M2: Anti-inflammatory macrophage; CCL2: C-C motif chemokine ligand 2; CCL21: C-C motif chemokine ligand 21; miRNA: MicroRNA.

Figure 3

Immunopathogenesis of rheumatoid arthritis and therapeutic effects of mesenchymal stem cells/mesenchymal stem cell-derived exosomes. Created with BioRender.com. Anti-CCP: Anti-cyclic citrullinated peptide; RA: Rheumatoid arthritis; MSCs: Mesenchymal stem cells; MSC-Exos: Mesenchymal stem cell-derived exosomes; TNF-α: Tumor necrosis factor-alpha; IL-4: Interleukin-4; IFN-γ: Interferon gamma; Treg: Regulatory T cell; Th1: T helper 1; Th17: T helper 17; TGF-β: Transforming growth factor-beta; CD4⁺ T cells: Cluster of differentiation 4 positive T cells; Breg: Regulatory B cells; MMP14: Matrix metalloproteinase-14; VEGF: Vascular endothelial growth factor; STAT3: Signal transducer and activator of transcription 3; lncRNA: Long non-coding RNA; FGL1: Fibrinogen-like protein 1; NF-κB: Nuclear factor kappa B; CXCL9: CXC motif chemokine ligand 9; M1: Pro-inflammatory macrophage; M2: Anti-inflammatory macrophage; miRNA: MicroRNA.