1. Human pluripotent stem cell-derived mesenchymal stem cells prevent chronic allergic airway inflammation via TGF-β1-Smad2/Smad3 signaling pathway in mice.
- Author
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Zhong H, Fan XL, Fang SB, Lin YD, Wen W, and Fu QL
- Subjects
- Animals, Bronchoalveolar Lavage Fluid, Chronic Disease, Cytokines metabolism, Disease Models, Animal, Female, Humans, Hypersensitivity complications, Hypersensitivity pathology, Mice, Inbred BALB C, Ovalbumin, Pneumonia complications, Pneumonia pathology, Signal Transduction, Hypersensitivity therapy, Induced Pluripotent Stem Cells cytology, Mesenchymal Stem Cell Transplantation, Mesenchymal Stem Cells cytology, Pneumonia therapy, Smad2 Protein metabolism, Smad3 Protein metabolism, Transforming Growth Factor beta1 metabolism
- 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., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
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