P064 Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism

Abstract

Abstract Background Conventional treatments for inflammatory bowel disease (IBD) have multiple potential side effects. Therefore, alternative treatments are desperately needed. Exosomes from mesenchymal stromal cells (MSC-Exos) show potent immunomodulatory activities and protective effects in several diseases. Methods MSC-Exos were isolated from human bone marrow-derived mesenchymal stromal cells. Experimental colitis was induced by administration of dextran sulphate sodium (DSS) in C57BL/6 mice (male, 6–8 weeks), or 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in Balb/c mice (male, 7–9 weeks). Macrophage depletion was performed via intraperitoneal injection of clodronate liposomes. Colitic mice were treated intravenously with MSC-Exos or saline, and mortality and diverse disease signs were tracked. Results Systemic administration of MSC-Exos significantly mitigated colitis in mice. MSC-Exos treatment downregulated inflammatory responses, maintained intestinal barrier integrity and polarised M2 macrophages. Infused MSC-Exos mainly acted on colonic macrophages and their beneficial effect was blocked by macrophage depletion. Particularly, MSC-Exos were enriched in proteins involved in regulating multiple biological processes associated with the anti-colitic benefit of MSC-Exos. Conclusion MSC-Exos are critical regulators of immune/inflammatory responses and may be promising candidates for IBD treatment