Avaliação do potencial terapêutico de vesículas extracelulares derivadas de células-tronco mesenquimais de cordão umbilical humano em modelo experimental de dermatite atópica em camundongos

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by eczematous lesions and intense pruritus, posing a significant public health challenge. Conventional therapies, primarily based on corticosteroids and immunosuppressants, have limited efficacy and are associated with significant adverse effects. The therapeutic use of mesenchymal stem cells (MSCs) or their secretome, including extracellular vesicles (VEs), has shown promising immunomodulatory effects in the treatment of immune-mediated diseases. In this study, the therapeutic potential of VEs derived from human umbilical cord MSCs was evaluated in BALB/c mice with atopic dermatitis induced by epicutaneous application of 2,4-dinitrochlorobenzene (DNCB). MSCs were isolated, characterized, and used to obtain VEs through ultracentrifugation. VEs were characterized by size, polydispersity index, zeta potential, and morphology using transmission electron microscopy. The results demonstrated that VEs significantly reduced inflammatory markers, such as the number of mast cells, epidermal thickness and pro-inflammatory cytokines IL-4 and TSLP, in addition to promoting the recovery of skin barrier integrity, evidenced by an increase in lipids in the stratum corneum. Histological analysis revealed superior epidermal organization in the treated groups, while clinical evaluation indicated significant improvement in lesions. In an in vitro model of keratinocyte activation, VEs modulated the gene expression of several genes associated with AD. The therapeutic effects observed were comparable to those of dexamethasone, establishing VEs as effective immunomodulatory agents. The findings underscore the potential of VEs derived from MSCs in the treatment of atopic dermatitis, offering an innovative and promising approach with a lower risk of adverse effects.