Healthy versus inflamed lung environments differentially effect MSCs

Sara Rolandsson Enes, Thomas H. Hampton, Jayita Barua, David H. McKenna, Claudia Dos Santos, Eyal Amiel, Alix Ashare, Kathleen D. Liu, Anna D. Krasnodembskaya, Karen English, Bruce Stanton, Patricia Rocco, Michael A. Matthay, Daniel Weiss

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Despite increased interest in MSC-based cell therapies for the acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and understanding of the potential in vivo mechanisms of MSC actions in ARDS remain 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: To comparatively assess how the inflammatory environment present in ARDS lungs versus the lung environment present in healthy volunteers alters MSC behaviors.

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 HLA expression, and activation of coagulation and complement pathways.

Results: Pro-inflammatory, pro-coagulant, and major histocompatibility complex (self recognition) related gene expression was markedly up-regulated in hMSCs exposed ex vivo to BALF obtained from healthy volunteers. In contrast, 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 strongly suggesting that the inflamed environment in ARDS induces hMSC responses potentially benefical for cell survival and actions. This further highlights the need to understand how different disease environments affect hMSC functions.
Original languageEnglish
JournalEuropean Respiratory Journal
Early online date01 Apr 2021
DOIs
Publication statusEarly online date - 01 Apr 2021

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