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Publication : Mesenchymal stem cells exert their anti-asthmatic effects through macrophage modulation in a murine chronic asthma model.

First Author  Kim RL Year  2022
Journal  Sci Rep Volume  12
Issue  1 Pages  9811
PubMed ID  35697721 Mgi Jnum  J:341502
Mgi Id  MGI:7293849 Doi  10.1038/s41598-022-14027-x
Citation  Kim RL, et al. (2022) Mesenchymal stem cells exert their anti-asthmatic effects through macrophage modulation in a murine chronic asthma model. Sci Rep 12(1):9811
abstractText  Despite numerous previous studies, the full action mechanism of the pathogenesis of asthma remains undiscovered, and the need for further investigation is increasing in order to identify more effective target molecules. Recent attempts to develop more efficacious treatments for asthma have incorporated mesenchymal stem cell (MSC)-based cell therapies. This study aimed to evaluate the anti-asthmatic effects of MSCs primed with Liproxstatin-1, a potent ferroptosis inhibitor. In addition, we sought to examine the changes within macrophage populations and their characteristics in asthmatic conditions. Seven-week-old transgenic mice, constitutively overexpressing lung-specific interleukin (IL)-13, were used to simulate chronic asthma. Human umbilical cord-derived MSCs (hUC-MSCs) primed with Liproxstatin-1 were intratracheally administered four days prior to sampling. IL-13 transgenic mice demonstrated phenotypes of chronic asthma, including severe inflammation, goblet cell hyperplasia, and subepithelial fibrosis. Ly6C(+)M2 macrophages, found within the pro-inflammatory CD11c(+)CD11b(+) macrophages, were upregulated and showed a strong correlation with lung eosinophil counts. Liproxstatin-1-primed hUC-MSCs showed enhanced ability to downregulate the activation of T helper type 2 cells compared to naive MSCs in vitro and reduced airway inflammation, particularly Ly6C(+)M2 macrophages population, and fibrosis in vivo. In conclusion, intratracheal administration is an effective method of MSC delivery, and macrophages hold great potential as an additional therapeutic target for asthma.
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