Extracellular vesicles from adipose stem cells ameliorate allergic rhinitis in mice by immunomodulatory

Wenhan Yang; Zhiyu Pan; Jiacheng Zhang; Lian Wang; Ju Lai; Shican Zhou; Zhili Zhang; Kai Fan; Dan Deng; Zhengliang Gao; Shaoqing Yu

doi:10.3389/fimmu.2023.1302336

Extracellular vesicles from adipose stem cells ameliorate allergic rhinitis in mice by immunomodulatory

Front Immunol. 2023 Dec 8:14:1302336. doi: 10.3389/fimmu.2023.1302336. eCollection 2023.

Authors

Wenhan Yang^#^{1

2}, Zhiyu Pan^#¹, Jiacheng Zhang¹, Lian Wang², Ju Lai^{1

2}, Shican Zhou^{1

2}, Zhili Zhang¹, Kai Fan¹, Dan Deng^{3

4}, Zhengliang Gao^{5

6

7}, Shaoqing Yu^{1

8}

Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
² School of Medicine, Tongji University, Shanghai, China.
³ Department of Dermatology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁴ Department of Dermatology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Fundamental Research Center, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China.
⁶ Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, Shanghai, China.
⁷ Institute of Geriatrics (Shanghai University), Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), School of Medicine, Shanghai University, Nantong, China.
⁸ Department of Allergy, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.

^# Contributed equally.

Abstract

Background: Human adipose tissue-derived stem cells (hADSCs) exert potent immunosuppressive effects in the allogeneic transplantation treatment. In mouse model of allergic rhinitis (AR), ADSCs partially ameliorated AR. However, no study has evaluated the potential therapeutic effects of hADSC-derived extracellular vesicles (hADSC-EVs) on AR.

Methods: Female BALB/c mice were sensitized and challenged with ovalbumin (OVA) to induce AR. One day after the last nasal drop, each group received phosphate buffered saline (PBS) or hADSC-EVs treatment. Associated symptoms and biological changes were then assessed.

Results: hADSC-EV treatment significantly alleviated nasal symptoms, and reduced inflammatory infiltration. Serum levels of OVA-specific IgE, interleukin (IL)-4 and interferon (IFN)-γ were all significantly reduced. The mRNA levels of IL-4 and IFN-γ in the spleen also changed accordingly. The T helper (Th)1/Th2 cell ratio increased. The treatment efficacy index of hADSC-EV was higher than that of all human-derived MSCs in published reports on MSC treatment of AR. ADSC-EVs exhibited a greater therapeutic index in most measures when compared to our previous treatment involving ADSCs.

Conclusion: These results demonstrated that hADSC-EVs could ameliorate the symptoms of AR by modulating cytokine secretion and Th1/Th2 cell balance. hADSC-EVs could potentially be a viable therapeutic strategy for AR. Further animal studies are needed to elucidate the underlying mechanisms and to optimize potential clinical protocols.

Keywords: Th1 and Th2 cells; allergic rhinitis; anti-inflammation; extracellular vesicles; human adipose tissue-derived stem cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cytokines*
Female
Humans
Immunoglobulin E
Mice
Rhinitis, Allergic*
Stem Cells
T-Lymphocytes, Helper-Inducer

Substances

Cytokines
Immunoglobulin E

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Key R&D Program of China (2022YFC2504100), the National Science Foundation of China (No.81873689, No.82173396 and No.32070862), National Science Foundation of Shanghai (No. 23ZR1458000), Shanghai General Hospital Integrated Traditional Chinese and Western Medicine (No. ZHYY-ZXYJHZX-202118).