Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis

Abstract

Exosomes are nano-sized vesicles (30-200 nm) constantly released by almost all cells. The ability of exosomes to travel between cells and deliver their cargo, which includes lipids, proteins, and nucleic acids, makes them an appealing cell-free therapy option to treat multiple diseases. Here, we investigated for the first time whether human adipose tissue-derived mesenchymal stem cell-derived exosomes (ASC-exosomes) can ameliorate atopic dermatitis (AD) in an in vivo mouse model. When injected either intravenously (IV) or subcutaneously (SC) into NC/Nga mice treated with house dust mite antigens, ASC-exosomes were found to reduce pathological symptoms such as clinical score, the levels of serum IgE, the number of eosinophils in blood, and the infiltration of mast cells, CD86+, and CD206+ cells in skin lesions. ASC-exosomes also significantly reduced mRNA expression of various inflammatory cytokines such as interleukin (IL)-4, IL-23, IL-31, and tumor necrosis factor-α (TNF-α) in AD skin lesions of Nc/Nga mice. Taken together, these results suggest that ASC-exosomes can be a novel promising cell-free therapeutic modality for AD treatment.

Keywords: Adipose tissue-derived mesenchymal stem cells; Atopic dermatitis; Exosome; Inflammation.

Fig. 1

Therapeutic effects of ASC-exosomes on AD-like lesions in NC/Nga mice. a The study protocol. b Representative skin manifestations in NC/Nga mice at days 0 and 28, H&E staining results, toluidine blue staining results, and immunohistochemical staining of CD86+ or CD206+ cells of ear skin samples from AD mice. Enlarged images of toluidine blue staining for mast cells and immunostaining for CD86 and CD206 are shown in Additional file 1: Figures S4–S6, respectively. Indicated amounts of ASC-exosomes (micrograms/head) were administered either by IV or SC thrice a week for 4 weeks. c Relative percentage improvement of clinical skin severity scores compared to vehicle group. Percentage improvement was calculated as described in Additional file 1: Materials and methods. d Improvement of ear thickness as measured in H&E-stained tissue sections in b. e The number of mast cells in the skin lesions determined in toluidine blue-stained tissue sections in b. Quantitative analysis of CD86+ (f) and CD206+ (g) cells as determined in tissue sections in b. Results are presented as mean ± standard error of the mean; n = 10 for each group. *P < 0.05, **P < 0.01, and ***P < 0.001 vs vehicle control group. IV intravenous administration, SC subcutaneous administration, Pred prednisolone

Fig. 2

The effect of ASC-exosomes on the level of serum IgE, the number of eosinophils, and the expression of pro-inflammatory cytokines in NC/Nga mice. a The level of serum IgE was detected by ELISA. b The number of eosinophils in blood was determined by differential cell counting. c–f Total RNA was isolated and the mRNA levels of IL-4 (c), IL-31 (d), TNF-α (e), and IL-23 (f) were detected by quantitative real-time PCR and normalized by GAPDH mRNA expression. Results are presented as mean ± standard error of the mean; n = 10. *P < 0.05, **P < 0.01, and ***P < 0.001 vs vehicle group. IV intravenous administration, SC subcutaneous administration, Pred prednisolone