Rolandsson Enes, Sara and Hampton, Thomas H. and Barua, Jayita and McKenna, David H. and dos Santos, Claudia C. and Amiel, Eyal and Ashare, Alix and Liu, Kathleen D. and Krasnodembskaya, Anna D. and English, Karen and Stanton, Bruce A. and Rocco, Patricia R.M. and Matthay, Michael A. and Weiss, Daniel J. (2021) Healthy versus inflamed lung environments differentially affect mesenchymal stromal cells. European Respiratory Journal, 58 (200414). pp. 1-14. ISSN 0903-1936

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Abstract

Background Despite increased interest in mesenchymal stromal cell (MSC)-based cell therapies for acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and our understanding of the potential in vivo mechanisms of MSC actions in ARDS remains limited. ARDS is driven by an acute severe innate immune dysregulation, often characterised by inflammation, coagulation and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined. Aim The aim of this study was to comparatively assess how the inflammatory environment present in ARDS lungs versus the lung environment present in healthy volunteers alters MSC behaviour. Methods Clinical-grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients or from healthy volunteers. Following exposure, hMSCs and their conditioned media were evaluated for a broad panel of relevant properties, including viability, levels of expression of inflammatory cytokines, gene expression, cell surface human leukocyte antigen expression, and activation of coagulation and complement pathways. Results Pro-inflammatory, pro-coagulant and major histocompatibility complex (self-recognition) related gene expression was markedly upregulated in hMSCs exposed ex vivo to BALF obtained from healthy volunteers. These changes were less apparent and often opposite in hMSCs exposed to ARDS BALF samples. Conclusion These data provide new insights into how hMSCs behave in healthy versus inflamed lung environments, and strongly suggest that the inflamed environment in ARDS induces hMSC responses that are potentially beneficial for cell survival and actions. This further highlights the need to understand how different disease environments affect hMSC functions.

Item Type:	Article
Keywords:	Healthy; versus; inflamed; lung; environments; differentially affect; mesenchymal stromal cells;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17116
Identification Number:	https://doi.org/10.1183/13993003.04149-2020
Depositing User:	Karen English
Date Deposited:	24 Apr 2023 14:43
Journal or Publication Title:	European Respiratory Journal
Publisher:	European Respiratory Society
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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