RT Journal Article SR Electronic T1 ARDS disease-relevant cytokines alter human mesenchymal stromal cell (MSC) function JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP PA5236 DO 10.1183/13993003.congress-2023.PA5236 VO 62 IS suppl 67 A1 Rolandsson Enes, Sara YR 2023 UL https://publications.ersnet.org//content/62/suppl_67/PA5236.abstract AB Introduction: Mesenchymal stromal cells (MSC)-based therapies have advanced into clinical settings in several diseases including ARDS. Yet, no significant outcome has been demonstrated. Increasing evidence suggests that MSCs alter their therapeutic functions when exposed to external factors including the local inflammatory environments. ARDS is a clinical syndrome that includes at least 2 phenotypes (hyper- and hypo-inflammation) with very different clinical pathways. However, it is still unknown if any of the phenotypes are more beneficial for MSC-based therapies, or if the underlaying biology of these phenotypes alter MSC functions. Therefore, the aim of this study was to test the effect of ARDS disease-relevant cytokines on human bone marrow-derived MSC function (hMSCs).Methods: hMSCs were exposed to disease-relevant cytokines for 1 or 24 hours. Gene and protein expression will be analyzed on exposed hMSCs and compared to control cells. Conditioned medium was collected for determination of the secretome profiles, immune-regulatory functions, and cytotoxicity analyzes.Results: Preliminary data suggests that hMSCs exposed to cytokines highly abundant in ARDS patients with a hyperinflammatory sub-phenotype had increased metabolic activity, increased proliferation rate, and altered secretome profile compared to hMSCs exposed to medium alone. Conditioned medium was collected and functional immunoregulatory studies are currently ongoing.Conclusions: A better understanding on how the microenvironment in patients with different ARDS sub-phenotypes influence hMSCs functions will help us to better design clinical trials and increase the success rate of MSC-based therapies of ARDS.FootnotesCite this article as: European Respiratory Journal 2023; 62: Suppl. 67, PA5236.This abstract was presented at the 2023 ERS International Congress, in session “Inflammatory endotyping: the macrophage across disease areas”.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).