Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells
| Autor: | Soraia C. Abreu, Robert A. Cramer, Dwight E. Matthews, Eyal Amiel, David H. McKenna, Alix Ashare, Karatatiwant Singh Sidhu, Fernanda F. Cruz, Anna Krasnodembskaya, Patricia R. M. Rocco, Jayita Barua, Evan T Hoffman, Bruce A Stanton, Jacob Dearborn, Michael A. Matthay, Bernard P. Mahon, Matthew J. Wargo, Claudia C. dos Santos, Thomas H. Hampton, Karen English, Daniel C. Chambers, Sara Rolandsson Enes, Daniel J. Weiss, Kathleen D. Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Physiology gliotoxin Cell Anti-Inflammatory Agents Mesenchymal Stem Cell Transplantation Cystic fibrosis Cell therapy cystic fibrosis 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being In vivo Physiology (medical) medicine Humans Lung medicine.diagnostic_test business.industry Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology respiratory system medicine.disease 3. Good health respiratory tract diseases 030104 developmental biology Bronchoalveolar lavage medicine.anatomical_structure 030228 respiratory system Aspergillus infection Immunology mesenchymal stromal cell cell therapy business Bronchoalveolar Lavage Fluid Ex vivo Research Article |
| Zdroj: | Abreu, S, Hampton, T, Hoffman, E, Dearborne, J, Ashare, A, Sidhu, K, Mattheews, D, McKenna, D, Amiel, E, Barua, J, Krasnodembskaya, A, English, K, Mahon, B P, Dos Santos, C, Cruz, F, Chambers, D, Liu, K D, Matthay, M A, Cramer, R, Stanton, B, Rocco, P, Wargo, M, Weiss, D & Rolandsson Enes, S 2020, ' Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells. ', American Journal of Physiology-Lung Cellular and Molecular Physiology . https://doi.org/10.1152/ajplung.00218.2020 American Journal of Physiology-Lung Cellular and Molecular Physiology |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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