Adipose-Derived Stem Cell Exosomes Inhibit Hypertrophic Scaring Formation by Regulating Th17/Treg Cell Balance

Aiming to reveal the role of ADCS-Exos in secretion of inflammatory factors, Th17 and regulatory T (Treg) cell differentiation from naive CD4+ T cells in hypertrophic scaring formation and maturation is explored. ELISA, qRT-PCR, and immunoblotting are performed to assay the local inflammatory factors IL-6, IL-10, IL-17A, and TNF-alpha, and transcriptional factors of ROR Upsilon t and Foxp3, in scaring tissue from patients and mice wound models treated with or without ADCS-Exos. Immunohistochemistry staining and immunoblotting are conducted to assay the extracellular matrix (ECM) deposition in vitro and in vivo. The results show that IL-6, IL-10, IL-17A, TNF-alpha, ROR Upsilon t, and Foxp3 are increased on mRNA and protein levels in hypertrophic scaring compared with atrophic scaring and normal skin. Naive CD4(+) T cells treated with ADCS-Exos in vitro can produce significantly less IL-6, IL-17A, TNF-alpha, and ROR Upsilon t and more IL-10 and Foxp3 on mRNA and protein levels. In addition, mice in ADSGExos-treated group demonstrate less collagen deposition; decreased IL-17A, TNF-alpha, and ROR Upsilon t; and increased IL-10 and Foxp3 production.