Authors: Sara Rolandsson Enes, Thomas H. Hampton, Jayita Barua, David H. McKenna, Claudia C. dos Santos, Eyal Amiel, Alix Ashare, Kathleen D. Liu, Anna D. Krasnodembskaya, Karen English, Bruce A. Stanton, Patricia R.M. Rocco, Michael A. Matthay, Daniel J. Weiss
Published: 2021-04-01
DOI: 10.1183/13993003.04149-2020
Source: Full article
BackgroundDespite 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 potentialin vivomechanisms 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.AimThe aim of this study was to comparatively assess how the inflammatory environment present in ARDS lungsversusthe lung environment present in healthy volunteers alters MSC behaviour.MethodsClinical-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.ResultsPro-inflammatory, pro-coagulant and major histocompatibility complex (self-recognition) related gene expression was markedly upregulated in hMSCs exposedex vivoto BALF obtained from healthy volunteers. These changes were less apparent and often opposite in hMSCs exposed to ARDS BALF samples.ConclusionThese data provide new insights into how hMSCs behave in healthyversusinflamed 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.