Human umbilical cord mesenchymal stem cell therapy for atopic dermatitis through inhibition of neutrophil chemotaxis.

BACKGROUND: Atopic dermatitis (AD) management is significantly challenging due to the high prevalence, chronicity, and recurrent nature of the disease, and limited options for its treatment. Human umbilical cord mesenchymal stem cells (hUC-MSCs) exhibit potential effects against AD; however, the mechanisms underlying these effects remain largely unexplored. METHODS: AD mouse models were established using 1-chloro-2,4-dinitrobenzene (DNCB) and ovalbumin (OVA). The therapeutic effects of subcutaneously administered hUC-MSCs and their conditioned medium (hUC-MSC-CM) were evaluated through histopathology, western blotting, PCR, ELISA, and flow cytometry. Mechanistic studies included RNA sequencing, cytokine arrays, and exosome characterization. RESULTS: Both hUC-MSCs and hUC-MSC-CM significantly alleviated AD-like symptoms, including erythema, epidermal thickening, and inflammatory cell infiltration in DNCB- and OVA-induced models. There was a decrease in serum IgE levels and histological analyses confirmed attenuated skin damage in these models. Moreover, neither hUC-MSCs nor hUC-MSC-CM induced weight loss. Mechanistically, hUC-MSC-CM suppressed neutrophil migration in the skin and inhibited keratinocyte-derived chemokine (e.g., CCL5 and CXCL11) secretion. Additionally, hUC-MSC-derived exosomes reduced chemokine production in keratinocytes, mediated by the STAT3 signaling pathway. CONCLUSIONS: This study demonstrated that hUC-MSCs and hUC-MSC-CM ameliorate AD-like symptoms, possibly through exosome-dependent suppression of the STAT3 signaling pathway and chemokine expression. Furthermore, hUC-MSC-CM serves as a cell-free alternative to whole-cell therapy, with comparable efficacy, offering novel mechanistic insights and a potential translational strategy for AD treatment.