Conditioned medium from stem cells of human exfoliated deciduous teeth ameliorates mouse ovalbumin-specific allergic dermatitis.

BACKGROUND

Atopic dermatitis (AD), a chronic inflammatory skin disease, is characterized by intense itching and recurrent eczema-like lesions, requiring safer, more targeted therapies that modulate the immune response and restore skin barrier integrity. Conditioned medium derived from stem cells of human exfoliated deciduous teeth (SHED-CM) exhibits considerable immunomodulatory and regenerative effects. We evaluated the efficacy of SHED-CM in an AD-like mouse model and explored the underlying mechanisms.

METHODS

Mice with ovalbumin (OVA)-specific allergic dermatitis (OSAD) were intravenously treated with SHED-CM, conditioned medium derived from fibroblast, or Dulbecco's Modified Eagle Medium, followed by antigen restimulation to induce AD-like dermatitis. Disease severity was assessed macroscopically and histologically. T cell phenotypes were analyzed using immunohistochemical staining, RT-qPCR, and flow cytometry. Total serum and OVA-specific immunoglobulin E (IgE) levels were measured using ELISA. Naïve splenic CD4⁺ T cells were activated using CD3/CD28 beads in SHED-CM to evaluate their direct effects on T cell differentiation through flow cytometry. Highly expressed proteins in SHED-CM were identified using liquid chromatography-mass spectrometry, and neutralizing antibodies were used to elucidate the therapeutic mechanisms.

RESULTS

The treatment with SHED-CM significantly ameliorated AD-like symptoms, reduced epidermal hyperplasia, and restored filaggrin expression. SHED-CM created an anti-inflammatory microenvironment in OSAD skin and draining lymph nodes by promoting Treg differentiation and inhibiting Th2 and Th17 populations. SHED-CM markedly suppressed B cell maturation, antigen-specific IgE production, and mast cell activation. Furthermore, we found that SHED-CM directly promoted Treg differentiation from naïve CD4⁺ T cells stimulated by CD3/CD28, which was mediated, in part, through TGFβ contained in SHED-CM. SHED-CM exhibited little to no effect on in vitro Th1, Th2, and Th17 differentiation.

CONCLUSIONS

SHED-CM shows significant therapeutic potential for AD-like symptom, effectively modulating immune response and enhancing skin barrier restoration. Our findings offer a new approach for developing novel, targeted therapies for inflammatory skin disorders.