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.