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Intranasal delivery of mesenchymal stem cell exosomes modulates the immune response of allergic rhinitis via the MAPK pathway in a mouse model
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  • Yin Chen,
  • Chenjie Yu,
  • Xinyun Xu,
  • Xin Dou,
  • Shuo Liu,
  • Handong Wang,
  • Xianmei Wei,
  • Zhengrong Xu,
  • Bin Wang,
  • Xin-Yan Cui,
  • Xia Gao
Yin Chen
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Chenjie Yu
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Xinyun Xu
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Xin Dou
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Shuo Liu
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Handong Wang
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Xianmei Wei
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Zhengrong Xu
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Bin Wang
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital
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Xin-Yan Cui
Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital
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Xia Gao
Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital

Corresponding Author:[email protected]

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Abstract

Background Allergic rhinitis (AR) is a non-infectious chronic inflammatory disease of the nasal mucosa, which is mainly mediated by IgE after the body is exposed to allergens. It has been shown that transplantation of human mesenchymal stem cells (MSCs) into AR animal models can improve the AR behavioral phenotype. Furthermore, there are recent studies that states exosomes are the main mediators of MSC therapy. However, the effect of exosomes on AR has not been investigated. Methods In the established AR mouse model, different concentrations of MSC-derived exosomes (MSCs-Exo) were applied via intranasal delivery. The AR symptom scores, the eosinophils in the nasal mucosal section, the inflammation infiltration in the spleen section, and IgE, ovalbumin-specific IgE (OVA-sIgE), histamine, IgG1, IgG2a and other Th1/Th2 related inflammatory factors were evaluated by Hematoxylin–eosin staining, Elisa, real-time PCR. Results We found that intranasal administration of MSCs-Exo could not only reduce the behavior of nasal scratching and sneezing in mice, but also cause a decline in related immune indicators via the MAPK pathway, including the spleen index, tissue staining, and the expression of inflammation-related cytokines. Moreover, we found that the optimal concentration of MSCs-Exo was 4×10 8/mL. Conclusion The significant beneficial effects of exosomes may be exploited to develop a new, non-invasive treatment strategy for AR.