P064 Exosomes from mesenchymal stromal cells reduce murine colonic inflammation via a macrophage-dependent mechanism
X.R. Wu1, P. Lan1, X.J. Wu1, X. Gao2
1The Sixth Affiliated Hospital of Sun Yat-sen University, Department of Colorectal Surgery, Guangzhou, China, 2The Sixth Affiliated Hospital of Sun Yat-sen University, Department of Gastroenterology, Guangdong, China
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