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

Differential effects of the cystic fibrosis lung inflammatory environment on mesenchymal stromal cells. Am J Physiol Lung Cell Mol Physiol. 2020 Sep 09;: Authors: Abreu SC, Hampton TH, Hoffman E, Dearborn J, Ashare A, Singh Sidhu K, Matthews DE, McKenna DH, Amiel E, Barua J, Krasnodembskaya A, English K, Mahon BP, Santos CD, Cruz FF, Chambers DC, Liu KD, Matthay MA, Cramer RA, Stanton BA, Rocco PRM, Wargo MJ, Weiss DJ, Rolandsson Enes S 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 ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research