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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Physiological Society
2020
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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. |
format | Online Article Text |
id | pubmed-7792680 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Physiological Society |
record_format | MEDLINE/PubMed |
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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