PT  - JOURNAL ARTICLE
AU  - Sara Rolandsson Enes
AU  - Thomas H. Hampton
AU  - David H. Mckenna
AU  - Claudia C. Dos Santos
AU  - Kathleen D. Liu
AU  - Bruce A. Stanton
AU  - Patricia R. M. Rocco
AU  - Michael A. Matthay
AU  - Daniel J. Weiss
TI  - Inflammatory microenvironment in both healthy controls and ARDS patients polarize clinically utilized MSCs towards a pro-inflammatory MSC phenotype
AID  - 10.1183/13993003.congress-2020.4473
DP  - 2020 Sep 07
TA  - European Respiratory Journal
PG  - 4473
VI  - 56
IP  - suppl 64
4099  - http://erj.ersjournals.com/content/56/suppl_64/4473.short
4100  - http://erj.ersjournals.com/content/56/suppl_64/4473.full
SO  - Eur Respir J2020 Sep 07; 56
AB  - Background: Despite increased interest in MSC-based cell therapy to treat acute respiratory distress syndrome (ARDS), our understanding of the in vivo mechanisms of action of MSC are limited. ARDS is driven by an acute severe inflammatory response, but how this inflammatory microenvironment influences MSC therapeutic actions is at present unknown.Aim: To determine how the inflammatory environment present in ARDS lungs alters MSC behaviors, with comparison to healthy controls.Methods: Clinically utilized bone marrow-derived MSCs were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients without sepsis or healthy control subjects (HC). Following exposure, conditioned media were assessed for pro- and anti-inflammatory cytokines and gene expression profiles were analyzed using an RNA seq approach.Results: Following 24 hours of exposure, RNA seq analyses demonstrated that MSCs exposed to BALF samples, both ARDS and HC, induced a pro-inflammatory phenotype compared to saline-exposed control cells. Similar results were observed in conditioned media, with a significant increase production of IL-6, IL-8, and IL-18 in BALF exposed MSCs compared to saline control. Remarkably, the RNA seq data indicated that MSCs exposed to HC BALF were more potent in inducing a pro-inflammatory phenotype compared to ARDS BALF samples.Conclusion: Our data suggest that lung airspace environment in both healthy controls and ARDS patients may polarize MSCs towards a pro-inflammatory phenotype. These results highlight the need to understand how the alveolar environment of both normal and ARDS subjects can influence the phenotype of MSCs.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4473.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).