Adipose-Derived Stem Cell Secretome Attenuates Eosinophilic Inflammation in a Chronic Rhinosinusitis with Nasal Polyps Mouse Model.

Adipose-derived stem cells (ASCs) and their secretome have been reported to improve allergic airway inflammation. Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is characterized by type 2 helper T (Th2)-diven inflammation, which shares similar mechanisms with allergic airway diseases. We assessed the immunomodulatory effects of ASC secretome on an ECRSwNP mouse model. ECRSwNP was induced by ovalbumin (OVA) and Staphylococcus aureus enterotoxin B (SEB) intranasal challenges in five-week-old BALB/c mice. To evaluate the effect of ASC secretome on eosinophilic nasal inflammation, 10 μg/50 μL of ASC-conditioned media were administered three times a week during the eight weeks. H&E and Sirius red staining were performed to evaluate the formation of nasal polyps (NPs) and the infiltration of eosinophils. The cytokine levels of interleukin (IL)-4, IL-5, IL-13, interferon-γ, IL-8, and eotaxin-1 were measured using ELISA(eBiosciences, San Diego, CA, USA). The expression levels of IL-8 and eotaxin-1 mRNA were determined by quantitative PCR. Eosinophil cationic protein (ECP) and eotaxin-1 expression were assessed by immunohistochemistry. Intranasal administration of ASC secretome significantly decreased NP-like formation and eosinophilic infiltration in the sinonasal mucosa of ECRSwNP mice. The increased IL-4, IL-5, and eotaxin-1 levels after OVA + SEB challenge remarkably decreased by ASC secretome treatment. Furthermore, ASC secretome notably decreased the gene expression of eotaxin-1 by PCR, as well as ECP and eotaxin-1 expression by immunohistochemistry. ASC secretome had immunomodulatory effects in a mouse model of ECRSwNP. Intranasal administration of ASC secretome resulted in a significant reduction in NP formation and eosinophilic inflammation through the suppression of IL-4, IL-5, eotaxin-1, and ECP.