Effects of primed adipose mesenchymal stem cell‐derived exosomes on immunomodulation in Behcet uveitis

Aims/Purpose: Exosomes of interferon‐gamma (IFN‐ γ) primed (IFN + Exo) and non‐primed (IFN‐Exo) adipose‐derived mesenchymal stem cells (AdMSCs) were studied for their possible significance in the therapy of Behçet Disease (BD) uveitis (BU). Methods: Adipose tissue was used to isolate AdMSCs. Characterization as well as multipotency investigations were carried out. Exosomes of AdMSCs were also identified and characterized. Lymphocytes were isolated from the peripheral venous blood of patients with BD uveitis (n = 15) and healthy controls (n = 15). AdMSCs were preincubated for 48 h with or without IFN‐ γ. Peripheral Blood Mononuclear Cells (PBMC) of BD uveitis patients and healthy controls were cultivated with exosomes separately for 72 h. Flow cytometry was used to assess lymphocyte proliferation, viability, and apoptosis after the culture period. Real‐time polymerase chain reaction (RT‐PCR) was used to assess the expression of interleukin‐10 (IL‐10), interleukin‐17 (IL‐17), transforming growth factor‐ β (TGF‐ β), and interferon‐ γ (IFN‐ γ). Results: In patients with BD uveitis, IFN + Exo inhibited lymphocyte apoptosis. IFN + Exo reduced the viability of BD uveitis T lymphocytes. Both exosomes also raised IL‐10 level as an anti‐inflammatory cytokine and decreased IL‐17, TGF‐ β, IFN‐γ levels as a pro‐inflammatory cytokine in BD uveitis patients' lymphocytes. However, exosomes were ineffective in stimulating T lymphocyte proliferation. Conclusions: Exosomes of AdMSCs stimulated with and without IFN‐ γ decrease the abnormal inflammatory response caused by BD uveitis PBMC. This study's findings have the potential to pave the road for MSC/exosome therapy in BD uveitis.