Abreu, Soraia C. and Hampton, Thomas H. and Hoffman, Evan and Dearborn, Jacob and Ashare, Alix and Singh Sidhu, Karatatiwant and Matthews, Dwight E. and McKenna, David H. and Amiel, Eyal and Barua, Jayita and Krasnodembskaya, Anna and English, Karen and Mahon, Bernard P. and Dos Santos, Claudia and Cruz, Fernanda F. and Chambers, Daniel C. and Liu, Kathleen D. and Matthay, Michael A. and Cramer, Robert A. and Stanton, Bruce A. and Rocco, Patricia R. M. and Wargo, Matthew J. and Weiss, Daniel J. and Rolandsson Enes, Sara (2020) Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells. American Journal of Physiology-Lung Cellular and Molecular Physiology, 319 (6). L908-L925. ISSN 1040-0605

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Abstract

Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical bronchoalveolar lavage fluid (BALF) samples, as a surrogate for the in vivo clinical lung environment, on MSC viability, gene expression, secreted cytokines, and mitochondrial function were compared with effects of BALF collected from healthy volunteers. CF BALF samples that cultured positive for Aspergillus sp. (Asp) induced rapid MSC death, usually within several hours of exposure. Further analyses suggested the fungal toxin gliotoxin as a potential mediator contributing to CF BALF-induced MSC death. RNA sequencing analyses of MSCs exposed to either Asp+ or Asp− CF BALF samples identified a number of differentially expressed transcripts, including those involved in interferon signaling, antimicrobial gene expression, and cell death. Toxicity did not correlate with bacterial lung infections. These results suggest that the potential use of MSC-based cell therapies for CF or other lung diseases may not be warranted in the presence of Aspergillus.

Item Type:	Article
Keywords:	Aspergillus infection; cell therapy; cystic fibrosis; gliotoxin; mesen-chymal stromal cell;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	16137
Identification Number:	https://doi.org/10.1152/ajplung.00218.2020
Depositing User:	Karen English
Date Deposited:	20 Jun 2022 09:01
Journal or Publication Title:	American Journal of Physiology-Lung Cellular and Molecular Physiology
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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