Cytokine preconditioning enhances the therapeutic potential of MSCs in ARDS

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Rationale: Mesenchymal stem cell (MSC) therapy for acute respiratory distress syndrome (ARDS) has shown safety in clinical trials but efficacy remains unproven. Thus, MSC preconditioning has been proposed as a strategy to increase MSC efficacy. This project aims to explore the therapeutic enhancement of MSCs through preconditioning with a cytokine cocktail. Methods: Bone marrow-derived MSCs (BM-MSCs) were preconditioned with a cytokine cocktail (IL-1β, TNF-α and IFN-γ, 50ng/mL, “Cytomix”). Apoptosis and activation of the BM-MSCs were analysed by flow cytometry. Conditioned media (CM) was collected to quantify cytokine secretion by ELISA and to analyse the inhibitory effect of the MSC secretome on bacterial proliferation. Results: Compared to naïve BM-MSCs, the early and late apoptosis and necrosis induced by serum-free media decreased significantly in the Cytomix preconditioned group. The levels of surface markers CD54 and CD274 were significantly higher in Cytomix preconditioned BM-MSCs. In Cytomix preconditioned CM, higher levels of IL-6, IL-8 and MCP-1 were detected. Moreover, Cytomix preconditioning enhanced BM-MSC inhibitory effects on Klebsiella pneumoniae and Staphylococcus aureus. Conclusion: Cytomix preconditioning can enhance BM-MSC function, inducing resistance to starvation-induced apoptosis and necrosis, and regulates the phenotype of BM-MSCs to increase immunomodulatory properties. Besides this, cytomix preconditioning can augment the anti-microbial effects of BM-MSCs, which makes these preconditioned BM-MSCs a promising treatment for bacterial-induced ARDS.

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