دورية أكاديمية

Small extracellular vesicles derived from human mesenchymal stromal cells prevent group 2 innate lymphoid cell-dominant allergic airway inflammation through delivery of miR-146a-5p

التفاصيل البيبلوغرافية
العنوان: Small extracellular vesicles derived from human mesenchymal stromal cells prevent group 2 innate lymphoid cell-dominant allergic airway inflammation through delivery of miR-146a-5p
المؤلفون: Shu-Bin Fang, Hong-Yu Zhang, Cong Wang, Bi-Xin He, Xiao-Qing Liu, Xiang-Ci Meng, Ya-Qi Peng, Zhi-Bin Xu, Xing-Liang Fan, Zhang-Jin Wu, Dong Chen, Lei Zheng, Song Guo Zheng, Qing-Ling Fu
المصدر: Journal of Extracellular Vesicles, Vol 9, Iss 1 (2020)
بيانات النشر: Wiley, 2020.
سنة النشر: 2020
المجموعة: LCC:Cytology
مصطلحات موضوعية: small extracellular vesicles, exosomes, mesenchymal stromal cells, anion-exchange chromatography, scalable protocol, group 2 innate lymphoid cells, allergic airway inflammation, microrna, Cytology, QH573-671
الوصف: Group 2 innate lymphoid cells (ILC2s) are recently reported to play a more critical role in allergic diseases. We previously identified that mesenchymal stromal cells (MSCs) elicited therapeutic effects on allergic airway inflammation. Small extracellular vesicles (sEV) derived from MSCs possess striking advantages including low immunogenicity and high biosafety, and is extremely promising cell-free therapeutic agents. However, the effects of MSC-sEV on ILC2s are still unclear. Additionally, scalable isolation protocols are required for the mass production of homogenous MSC-sEV especially in clinical application. We previously reported that induced pluripotent stem cells-derived MSCs were the ideal cellular source for the large preparation of MSC-sEV. Here we developed a standardized scalable protocol of anion-exchange chromatography for isolation of MSC-sEV, and investigated the effects of MSC-sEV on ILC2 function from patients with allergic rhinitis and in a mouse ILC2-dominant asthma model. The characterization of MSC-sEV was successfully demonstrated in terms of size, morphology and specific markers. Using flow cytometry and human Cytokine Antibody Array, MSC-sEV but not fibroblasts-sEV (Fb-sEV) were found to significantly inhibit the function of human ILC2s. Similarly, systemic administration of MSC-sEV but not Fb-sEV exhibited an inhibition of ILC2 levels, inflammatory cell infiltration and mucus production in the lung, a reduction in levels of T helper 2 cytokines, and alleviation of airway hyperresponsiveness in a mouse model of asthma. Using RNA sequencing, miR-146a-5p was selected as the candidate to mediate the above effects of MSC-sEV. We next revealed the uptake of ILC2s to MSC-sEV, and that transfer of miR-146a-5p in MSC-sEV to ILC2s in part contributed to the effects of MSC-sEV on ILC2s in vitro and in a mouse model. In conclusion, we demonstrated that MSC-sEV were able to prevent ILC2-dominant allergic airway inflammation at least partially through miR-146a-5p, suggesting that MSC-sEV could be a novel cell-free strategy for the treatment of allergic diseases.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2001-3078
20013078
العلاقة: https://doaj.org/toc/2001-3078Test
DOI: 10.1080/20013078.2020.1723260
الوصول الحر: https://doaj.org/article/b53ca304d7724595ad9e60847754c34cTest
رقم الانضمام: edsdoj.b53ca304d7724595ad9e60847754c34c
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20013078
DOI:10.1080/20013078.2020.1723260