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

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 ex...

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Autores principales: Abreu, Soraia C., Hampton, Thomas H., Hoffman, Evan, Dearborn, Jacob, Ashare, Alix, Singh Sidhu, Karatatiwant, Matthews, Dwight E., McKenna, David H., Amiel, Eyal, Barua, Jayita, Krasnodembskaya, Anna, English, Karen, Mahon, Bernard, Dos Santos, Claudia, Cruz, Fernanda F., Chambers, Daniel C., Liu, Kathleen D., Matthay, Michael A., Cramer, Robert A., Stanton, Bruce A., Rocco, Patricia R. M., Wargo, Matthew J., Weiss, Daniel J., Rolandsson Enes, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Physiological Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792680/
https://www.ncbi.nlm.nih.gov/pubmed/32901521
http://dx.doi.org/10.1152/ajplung.00218.2020
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author Abreu, Soraia C.
Hampton, Thomas H.
Hoffman, Evan
Dearborn, Jacob
Ashare, Alix
Singh Sidhu, Karatatiwant
Matthews, Dwight E.
McKenna, David H.
Amiel, Eyal
Barua, Jayita
Krasnodembskaya, Anna
English, Karen
Mahon, Bernard
Dos Santos, Claudia
Cruz, Fernanda F.
Chambers, Daniel C.
Liu, Kathleen D.
Matthay, Michael A.
Cramer, Robert A.
Stanton, Bruce A.
Rocco, Patricia R. M.
Wargo, Matthew J.
Weiss, Daniel J.
Rolandsson Enes, Sara
author_facet Abreu, Soraia C.
Hampton, Thomas H.
Hoffman, Evan
Dearborn, Jacob
Ashare, Alix
Singh Sidhu, Karatatiwant
Matthews, Dwight E.
McKenna, David H.
Amiel, Eyal
Barua, Jayita
Krasnodembskaya, Anna
English, Karen
Mahon, Bernard
Dos Santos, Claudia
Cruz, Fernanda F.
Chambers, Daniel C.
Liu, Kathleen D.
Matthay, Michael A.
Cramer, Robert A.
Stanton, Bruce A.
Rocco, Patricia R. M.
Wargo, Matthew J.
Weiss, Daniel J.
Rolandsson Enes, Sara
author_sort Abreu, Soraia C.
collection PubMed
description 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.
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spelling pubmed-77926802021-12-01 Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells Abreu, Soraia C. Hampton, Thomas H. Hoffman, Evan Dearborn, Jacob Ashare, Alix Singh Sidhu, Karatatiwant Matthews, Dwight E. McKenna, David H. Amiel, Eyal Barua, Jayita Krasnodembskaya, Anna English, Karen Mahon, Bernard Dos Santos, Claudia Cruz, Fernanda F. Chambers, Daniel C. Liu, Kathleen D. Matthay, Michael A. Cramer, Robert A. Stanton, Bruce A. Rocco, Patricia R. M. Wargo, Matthew J. Weiss, Daniel J. Rolandsson Enes, Sara Am J Physiol Lung Cell Mol Physiol Research Article 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. American Physiological Society 2020-12-01 2020-09-09 /pmc/articles/PMC7792680/ /pubmed/32901521 http://dx.doi.org/10.1152/ajplung.00218.2020 Text en Copyright © 2020 The Authors http://creativecommons.org/licenses/by/4.0/deed.en_US Licensed under Creative Commons Attribution CC-BY 4.0 (http://creativecommons.org/licenses/by/4.0/deed.en_US) : © the American Physiological Society.
spellingShingle Research Article
Abreu, Soraia C.
Hampton, Thomas H.
Hoffman, Evan
Dearborn, Jacob
Ashare, Alix
Singh Sidhu, Karatatiwant
Matthews, Dwight E.
McKenna, David H.
Amiel, Eyal
Barua, Jayita
Krasnodembskaya, Anna
English, Karen
Mahon, Bernard
Dos Santos, Claudia
Cruz, Fernanda F.
Chambers, Daniel C.
Liu, Kathleen D.
Matthay, Michael A.
Cramer, Robert A.
Stanton, Bruce A.
Rocco, Patricia R. M.
Wargo, Matthew J.
Weiss, Daniel J.
Rolandsson Enes, Sara
Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
title Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
title_full Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
title_fullStr Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
title_full_unstemmed Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
title_short Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
title_sort differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792680/
https://www.ncbi.nlm.nih.gov/pubmed/32901521
http://dx.doi.org/10.1152/ajplung.00218.2020
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