In this study human adipose tissue derived mesenchymal stem cell derived exosomes are investigated for the first known time to determine if whether they can ameliorate atopic dermatitis in an in vivo model mouse. When injected intravenously or subcutaneously into NC/Nga mice treated with house dust mite agents, ASC exosomes were found to reduce pathological symptoms such as levels of serum IgE, number of eosinophils in the blood, CD86+, infiltration of mast cells, clinical score, and CD206+ in skin lesions. MRNA expression of various inflammatory cytokines such as interleukin IL23, IL31, and tumor necrosis factor-a in AD skin lesions of Nc/Nga mice were also decreased. Combined findings suggest that ASC exosomes may be a promising cell free therapeutic modality for atopic dermatitis.
Current treatment options for atopic dermatitis are limited and can have potentially harmful side effects. Several biologics targeting pro-inflammatory cytokines are under development and dupilumab was recently approved by the USA FDA for adults with moderate to severe atopic dermatitis. Long term follow up studies are required to determine late side effects of dupilumab with efficacy suggesting multiple targeting is a plausible method to treat atopic dermatitis.
Studies have suggested that allergic progress in atopic dermatitis may be suppressed by mesenchymal stem cells derived from human umbilical cord blood, bone marrow, or adipose tissue by modulating multiple targets. Therapeutic targets uses of mesenchymal stem cells has drawbacks including poor engraftment efficiency, unwanted immune responses, potential tumor formation, short half life, non-specific differentiation, and difficulty of quality control before administration.
Exosomes are nanovesicle released by most cells found in all body fluids that deliver their cargo from origination cells to recipient cells. Evidence suggests exosomes derived from stem cells may be a promising alternative to cell based therapy as they would avoid most problems associated with cell based therapies while recapitulating therapeutic efficacy of stem cells, that can be sterilized by filtration and have longer shelf lives. Being smaller in size than stem cells exosomes can easily circulate through the body to reach injury sites, and long term repetitive administration does not elicit toxicity.
To investigate whether ASC exosomes could ameliorate atopic dermatitis symptoms in vivo effects of ASC-exosomes were evaluated in a murine model. Lesion were induced and treated with ASC exosomes subcutaneously or intravenously three times a week for 4 weeks, with oral prednisolone administered daily in positive controls. IV and SC administration of ASC exosomes were found to decrease symptoms in dose dependent manners. In treated mice, ear thickness was reduced, numbers of infiltrated mast cells was decreased, CD86+ and CD206+ cells decreased in skin lesions, and eosinophils and serum IgE levels were reduced after treatment having had little effect on neutrophil or white blood cell numbers. MRNA levels of inflammatory cytokines were analyzed via real time PCR, administration reduced up-regulated mRNA levels in skin lesions comparable to prednisolone correlated with alleviation of symptoms.
Collective data demonstrates systemic administration of ASC exosomes ameliorates atopic dermatitis like symptoms via regulation of inflammatory response and expression of inflammatory cytokines, indicating that ASC exosomes may be a novel cell free therapeutic strategy for the treatment of atopic dermatitis.
This study is limited to the potential of donor variability remaining to be addressed, and that donor age negatively impacts immuno-modulatory properties of ASC. Additional studies are required to confirm findings and whether potency of ASC exosomes from aged donors correlates with observation in younger healthy donors.
