Objective: We sought to evaluate the immunomodulatory effects of tonsil derived mesenchymal stem cells (T-MSC) in a mouse model of eosinophilic rhinosinusitis with nasal polyp(ERSwNP)
Methods: The effect of T-MSCs was evaluated in 32 BALB/c mice that were randomly divided into 4 groups (negative control group; nasal polyp group; T-MSC group and T-MSC(AD) group(T-MSC incubated with adipogenic differentiated medium)). After induction of OVA- induced ERSwNP model, T-MSCs were administered intravenously (T-MSC and T-MSC(AD) groups) on weeks5 to 12 (one time per week)and subsequent OVA+SEB (three times per week in OVA and one time per week in SEB) challenge was conducted until 12 weeks.We studied mRNA and protein expression profiles of cytokine, chemokine and adhesion molecules in nasal mucosa, spleen and lymphnode using molecular, biochemical, histopathologicaland immunohistological methods.
Results:Intravenous injection of T-MSCs significantly reduced allergic symptoms, eosinophil, neutrophil, nasal polyp count and serum OVA specific-IgG1 levels. Moreover, the nasal, lymphnode and systemic Th2 cytokine profile and nasal innate cytokines such as IL-25 and IL-33, and chemokines (CCL11, CCL24, Cxcl1, CxCl2, ICAM1 and VCAM1) expression were reduced in T-MSCs injected groups, as compared to the nasal polyp group. Usually T-MSC(AD) group showed better inhibitory effects of inflammation than T-MSC group. In addition, our results showed that the T-MSCs injected groupssignificantly increased IL-10 and Treg positive cells (CD4+CD25+FoxP3+ cells) in cervical lymphnode, as compared to the nasal polyp group.
Conclusion:We demonstrate the administrationof T-MSCs effectively reduced polyp formation, inflammatory cell influx, cytokine profile, chemokine molecule expression, and T-cell subset distribution, suggestive of the mechanism of reduced CRS inflammation and less polyp formation in mouse model of ERSwNP. Therefore, T-MSC treatment is potentially an alternative therapeutic modality in CRSwNP.