Human pluripotent stem cell-derived mesenchymal stem cells prevent chronic allergic airway inflammation via TGF-β1-Smad2/Smad3 signaling pathway in mice. (May 2019)

• Record Type: Journal Article
• Authors: Zhong, Hua; Fan, Xing-Liang; Fang, Shu-Bin; Lin, Yong-Dong; Wen, Weiping; Fu, Qing-Ling
• Is Part Of: Molecular immunology. Volume 109(2019:May)
• Page Start: 51
• Page End: 57
• Publication Date: 2019-05
• Subjects: α-SMA α-smooth muscle actin -- AHR airway hyper-responsiveness -- ANOVA one-way analysis of variance -- BALF bronchoalveolar lavage fluid -- BM-MSCs bone marrow-derived mesenchymal stem cells -- ELISA enzyme-linked immunosorbent assay -- FITC fluorescein isothiocyanate -- H&E hematoxylin and eosin -- IL interleukin -- iPSC-MSCs mesenchymal stem cells derived from induced pluripotent stem cells -- OVA ovalbumin -- PAS periodic acid–Schiff -- PBS phosphate-buffered saline -- PE phycoerythrin -- Th2 type 2 T helper; Chronic asthma -- Human iPSC-MSCs -- Airway remodeling -- TGF-β1-Smad signaling pathway; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.02.017
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: iPSC-MSC administration effectively inhibits chronic allergic airway inflammation. iPSC-MSC administration prevents the airway remodeling. iPSC-MSCs may modulate chronic allergic airway inflammation via TGF-β1/Smad pathway. Abstract: Background: Asthma is a chronic disease involving inflamed airways, which were previously demonstrated, can be modulated by the mesenchymal stem cells derived from induced pluripotent stem cells (iPSC-MSCs). However, the long-term effects of iPSC-MSCs in inflamed airways are still unidentified. This study investigated the long-term effects and potential mechanisms involved in the immunomodulatory effects of iPSC-MSCs in the chronic mouse asthma model. Methods: Both human iPSC-MSCs and bone marrow (BM)-MSCs were transplanted into the long-term ovalbumin-induced mice before sensitization phase or during the challenge phase. Airway hyper-respnsiveness measurement, immunohistochemistry and ELISA were employed to assess the effects of MSCs. In addition, Smad2/3 levels were assessed by western blot analysis to investigate the possible mechanism involved. Results: The systemic administration of human iPSC-MSCs before the challenge protected the mice from the characters of the chronic allergic airway inflammation, in particular improving the airway remodeling and preventing fibrosis. In addition, the TGF-β1/Smad pathway was identified involved in the immunomodulatory effects of iPSC-MSCs on chronic allergic airway inflammation. Conclusions: The study demonstrated that iPSC-MSCs are capable of preventing chronic allergic airway inflammation over a prolonged period, which further proved the iPSC-MSC therapeutic potential for allergic airway inflammation in a clinical scenario.