Background Evidences suggest mesenchymal stem cells (MSC)-derived secretome (secretome) exert anti-inflammatory properties and could be used for the treatment of autoinflammatory diseases. This study aimed to investigate the efficacy of secretome on murine and human systemic lupus erythematosus (SLE).
Methods Fifty-two NZB/W F1 mice were randomly assigned into 4 groups (untreated, methylprednisolone, MSC, and secretome (n=13 for each group). The amount of proteinuria and histological damages, as well as renal deposition of immune-complexes was assessed. Serum cytokines and anti-dsDNA levels were determined by ELISA. Helper T (Th) cell, dendritic cell, macrophage, and plasma cell markers were analyzed using flow cytometry. CD4+ T cells from SLE patients were cultured with secretome to identify the effect of secretome ex vivo.
Results Mice treated with methylprednisolone, MSC, and secretome exhibited diminished proteinuria, improved renal injury, and reduced renal deposition of immune-complexes compared to untreated mice. Regarding Th cell subsets, the proportion of Th1 and Th2 cells decreased and regulatory T cells (Tregs) increased in splenocytes from secretome treated mice. In addition, expression of mature dendritic cells and plasma cells in splenocytes, as well as M1 macrophages in the peritoneum decreased following secretome treatment. Secretome treatment resulted in a decrease of serum cytokines of interferon-γ, interleukin (IL)-17A, and anti-dsDNA, whereas IL-10 level was increased. No toxic effect of secretome was shown in mice. Treatment of CD4+ T cells isolated from SLE patients with secretome induced an increase of Tregs.
Conclusions Our results suggest secretome could be a promising therapeutic agent for SLE.
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