The inflammatory microenvironment in ARDS patients affects the metabolism of MSCs

<bold>Background:</bold> Mesenchymal stem cells (MSCs) have demonstrated promise in animal models of acute respiratory distress syndrome (ARDS), however clinical results have yet to show significant efficacy. Previous research has shown that for MSCs to have an effective immunomodulatory capacity, they need a metabolic switch toward glycolysis (Li, Dai et al. 2023). However, no published studies have assessed the implications of the ARDS microenvironment on the metabolism of MSCs, which can have an impact on their immunomodulatory function. <bold>Aim:</bold> This study sets out to investigate how the ARDS microenvironment modifies MSC metabolism in comparison with healthy control samples. <bold>Methods:</bold> Bone marrow-derived MSCs (BM-MSC) were cultured with either serum from COVID-19-ARDS patients or healthy control samples (HC). The serum samples were further grouped into hypo- and hyper-inflammatory phenotypes within the ARDS patient cohort. After exposure, the cells’ metabolic state was analysed using qPCR, flow cytometry, and colorimetric metabolic assays. <bold>Results:</bold> Preliminary results suggest that upon exposure to COVID-19 patient serum, the BM-MSCs had an increase in fatty acid oxidation and a decrease in glycolysis when compared to controls. This change was most significant after incubation with hyper-inflammatory serum. <bold>Conclusion:</bold> The results of this study support the idea that the ARDS microenvironment negatively affects the MSC through a metabolic change toward fatty acid oxidation. This research shows the importance of understanding the ARDS microenvironment and its effects on the MSC metabolic state.