Am J Physiol Lung Cell Mol Physiol. 2019 Sep 25. doi: 10.1152/ajplung.00263.2019. [Epub ahead of print]

Lung Inflammatory Environments Differentially Alter Mesenchymal Stromal Cell Behavior.

Abreu SC¹, Enes SR², Dearborn J², Goodwin M², Coffey A², Borg ZD², Dos Santos CC³, Wargo MJ⁴, Cruz FF⁵, Loi R⁶, DeSarno M⁷, Ashikaga T, Antunes MA¹, Rocco PRM⁸, Liu KD⁹, Lee JW¹⁰, Matthay MA¹¹, McKenna DH¹², Weiss DJ².

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.