Advanced

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

Abreu, Soraia Carvalho ; Hampton, Thomas H ; Hoffman, Evan ; Dearborn, Jacob ; Ashare, Alix ; Singh Sidhu, Karatatiwant ; Matthews, Dwight E ; McKenna, David H. ; Amiel, Eyal and Barua, Jayita , et al. (2020) In American Journal of Physiology: Lung Cellular and Molecular Physiology
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Lung Cellular and Molecular Physiology
publisher
American Physiological Society
external identifiers
  • pmid:32901521
  • scopus:85097003187
ISSN
1040-0605
DOI
10.1152/ajplung.00218.2020
language
English
LU publication?
yes
id
79229c20-c105-4e3d-b5d6-94a0818807a7
date added to LUP
2020-10-02 11:48:45
date last changed
2020-12-15 02:01:10
@article{79229c20-c105-4e3d-b5d6-94a0818807a7,
  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.},
  author       = {Abreu, Soraia Carvalho 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 Patrick and Santos, Claudia Dos 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},
  issn         = {1040-0605},
  language     = {eng},
  month        = {09},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Lung Cellular and Molecular Physiology},
  title        = {Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells},
  url          = {http://dx.doi.org/10.1152/ajplung.00218.2020},
  doi          = {10.1152/ajplung.00218.2020},
  year         = {2020},
}