Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells.

Soraia Abreu, Thomas Hampton, Evan Hoffman, Jacob Dearborne, Alix Ashare, Karatatiwant Sidhu, Dwight Mattheews, David McKenna, Eyal Amiel, Jayita Barua, Anna Krasnodembskaya, Karen English, Bernard P. Mahon, Claudia Dos Santos, Fernanda Cruz, Daniel Chambers, Kathleen D. Liu, Michael A. Matthay, Robert Cramer, Bruce StantonPatricia Rocco, Matthew Wargo, Daniel Weiss, Sara Rolandsson Enes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
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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 was compared to effects of BALF collected from healthy volunteers. CF BALF samples which 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, anti-microbial 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.
Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
DOIs
Publication statusPublished - 09 Sep 2020

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