Lung Inflammatory Environments Differentially Alter Mesenchymal Stromal Cell Behavior

Research output: Contribution to journalArticle

Abstract

Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally-induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow-derived MSCs (hMSCs) were exposed to in vitro culture conditions from bronchoalveolar lavage fluid (BALF) samples obtained from patients with either the acute respiratory distress syndrome (ARDS) or with other lung diseases including acute respiratory exacerbations of cystic fibrosis (CF) (non-ARDS). hMSCs were subsequently assessed for time- and BALF concentration-dependent effects on mRNA expression of selected pro- and anti-inflammatory mediators, and for overall patterns of gene and mRNA expression. Both common and disease specific-patterns were observed in gene expression of different hMSC mediators, notably interleukin (IL)-6. Conditioned media obtained from non-ARDS BALF-exposed hMSCs was more effective in promoting an anti-inflammatory phenotype in monocytes than was conditioned media from ARDS BALF-exposed hMSCs. Neutralizing IL-6 in the conditioned media promoted generation of anti-inflammatory monocyte phenotype. These results demonstrated that different lung inflammatory environments differentially alter hMSC behavior. Further identification of these interactions and the driving mechanisms may influence clinical use of MSCs for treating lung diseases.

Details

Authors
  • Soraia Carvalho Abreu
  • Sara Rolandsson Enes
  • Jacob Dearborn
  • Meagan Goodwin
  • Amy Coffey
  • Zachary D Borg
  • Claudia C Dos Santos
  • Matthew J Wargo
  • Fernanda Ferreira Cruz
  • Roberto Loi
  • Michael DeSarno
  • Takamaru Ashikaga
  • Mariana Alves Antunes
  • Patricia R M Rocco
  • Kathleen D Liu
  • Jae-Woo Lee
  • Michael A Matthay
  • D H McKenna
  • Daniel J Weiss
Organisations
External organisations
  • University of Vermont
  • University of Toronto
  • University of California, San Francisco
  • Federal University of Rio de Janeiro
  • University of Cagliari
  • University of Minnesota system
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
Original languageEnglish
Pages (from-to)L823-L831
Number of pages9
JournalAmerican Journal of Physiology: Lung Cellular and Molecular Physiology
Volume317
Issue number6
Early online date2019 Sep 25
Publication statusPublished - 2019 Dec 1
Publication categoryResearch
Peer-reviewedYes