Hypoxic hUCMSC-derived extracellular vesicles attenuate allergic airway inflammation and airway remodeling in chronic asthma mice

• DOI: 10.1186/s13287-020-02072-0
• Publication Date: 2021-01-06T18:03:54Z
• Authors: Liyang Dong; Ying Wang; Tingting Zheng; Yanan Pu; Yongbin Ma; Xin Qi; Wenzhe Zhang; Fei Xue; Zirui Shan; Jiameng Liu; Xuefeng Wang; Chaoming Mao
• Keywords: Masson's trichrome stain

Abstract Background As one of the main functional forms mesenchymal stem cells (MSCs), MSC-derived extracellular vesicles (MSC-EVs) have shown an alternative therapeutic option in experimental models allergic asthma. Oxygen concentration plays important role self-renewal, proliferation, and EV release MSCs a recent study found that anti-asthma effect was enhanced by culture hypoxic conditions. However, potential EVs (Hypo-EVs) asthma is still unknown. Methods BALB/c female mice were sensitized challenged with ovalbumin (OVA), each group received PBS, normoxic human umbilical cord MSC-EVs (Nor-EVs), or Hypo-EVs weekly. After treatment, animals euthanized, their lungs bronchoalveolar lavage fluid (BALF) collected. With use hematoxylin eosin (HE), periodic acid-Schiff (PAS) Masson’s trichrome staining, enzyme-linked immune sorbent assay (ELISA), Western blot analysis, real-time PCR, inflammation collagen fiber content airways lung parenchyma investigated. Results Hypoxic environment can promote (hUCMSCs) to more EVs. In OVA animals, administration Nor-EVs significantly ameliorated BALF total cells, eosinophils, pro-inflammatory mediators (IL-4 IL-13) asthmatic mice. Moreover, generally potent than suppressing airway Compared Nor-EVs, further prevented mouse chronic remodeling, concomitant decreased expression pro-fibrogenic markers α-smooth muscle actin (α-SMA), collagen-1, TGF-β1-p-smad2/3 signaling pathway. vitro, p-smad2/3, α-SMA, collagen-1 HLF-1 (human fibroblasts) stimulated TGF-β1. addition, we showed miR-146a-5p enriched compared Hypo-EV unregulated both tissues TGF-β1-treated HLF-1. More importantly, impaired Hypo-EV-mediated protection Conclusion Our findings provided first evidence hUCMSC-derived attenuated remodeling mice, potentially creating new avenues for treatment