Efficacy of Allogeneic and Xenogeneic Exosomes for the Treatment of Canine Atopic Dermatitis: A Pilot Study

Simple Summary Canine atopic dermatitis is a multifactorial allergic skin disease that lacks permanent curative treatment, and a single treatment strategy does not show efficacy in all cases. Therefore, novel and innovative therapeutic options are urgently needed. Exosomes, one of the major types of extracellular vesicles, have been investigated as an alternative treatment for various diseases in humans; however, the efficacy or side effects of exosomes in the treatment of canine atopic dermatitis are elusive. In this study, we investigated the therapeutic potential of canine- and human-derived exosomes against canine atopic dermatitis using six experimental models randomly assigned to control, canine exosome, or human exosome groups. Our findings revealed that canine- and human-derived exosomes alleviated canine atopic dermatitis in clinical, immunological, and microbiological aspects and that the treatment with exosomes was well tolerated.Abstract Canine atopic dermatitis (CAD) is a genetically predisposed inflammatory pruritic skin disease. The available treatments for CAD have several adverse effects and vary in efficacy, indicating the need for the development of improved treatments. In this study, we aimed to elucidate the therapeutic effects of allogeneic and xenogeneic exosomes on CAD. Six laboratory beagle dogs with CAD were randomly assigned to three treatment groups: control, canine exosome (cExos), or human exosome (hExos) groups. Dogs in the cExos and hExos groups were intravenously administered 1.5 mL of cExos (5 x 1010) and hExos (7.5 x 1011) solutions, respectively, while those in the control group were administered 1.5 mL of normal saline three times per week for 4 weeks. Skin lesion score and transepidermal water loss decreased in cExos and hExos groups compared with those in the control group. The exosome treatments decreased the serum levels of inflammatory cytokines (interferon-gamma, interleukin-2, interleukin-4, interleukin-12, interleukin-13, and interleukin-31) but increased those of anti-inflammatory cytokines (interleukin-10 and transforming growth factor-beta), indicating the immunomodulatory effect of exosomes. Skin microbiome analysis revealed that the exosome treatments alleviated skin bacterial dysbiosis. These results suggest that allogeneic and xenogeneic exosome therapy may alleviate CAD in dogs.