Abstract 247: Adipose-derived Stem Cells Suppress Aortic Inflammation and Aneurysm Expansion through Paracrine Mediated Mechanisms in an Elastase-induced Murine Model
Introduction: Abdominal aortic aneurysm (AAA) formation is characterized by activation of innate and adaptive immune responses that initiate aortic wall degradation. We hypothesize that human adipose stromal cells (ASC) favorably modulate these immune responses through paracrine mechanisms and attenuate AAA expansion in a murine elastase model.
Methods: AAA was induced in C57BL/6 mice by topical treatment of the abdominal aorta with elastase. Human ASC or saline was injected i.v. within 4 hours of elastase treatment. The aortic diameter was measured by ultrasound and video micrometry. Monocytes/macrophages and lymphocyte sub-populations cells were quantified by flow cytometry. Regulatory T cells (Treg) and M2 macrophages were quantified by immunohistochemical (IHC) staining. ASC were labeled with Hoechst and their distributions in the lung and aorta were imaged fluorescent microscopy and confirmed by real-time PCR for human-specific Alu sequence.
Results: ASC significantly suppressed AAA expansion at 14 days (n=10/group, p<0.01). At Day 1 there was a significant increase in Tregs in ASC treated mice(n=5/group, p<0.01) with a concurrent decrease of CD4+CD28-, CD8+CD28- T cells, and neutrophils (n=5/group, p<0.05). At Day 7, activated monocytes (insert CD16++?) and total aortic tissue resident macrophages were decreased (n=10/group, p<0.05) with a significant polarization to the tissue reparative M2 phenotype (n=5/group, p<0.05). Hoescht labeled ASC were detected in the lung without engraftment in the aorta at 24 hrs and were cleared at 96 hrs. Transmembrane co-culture of human peripheral blood mononuclear cells with ASCs induced Treg, polarize macrophages to the M2 phenoype, inhibited neutrophil transmigration, and suppressed lymphocyte proliferation, as further supporting the mechanism of paracrine immunomodulation in the in vivo model of AAA.
Conclusion: Systemic injection of ASC significantly suppresses AAA formation by inducing anti-inflammatory immune cell phenotypes. These effects are mediated by release of paracrine factors and suggest that further characterization of the ASC secretome may lead to more potent recombinant protein therapies for AAA.
Author Disclosures: M.P. Murphy: None. J. Xie: None. T. Jones: None. D. Feng: None. T.G. Cook: None. C.M. Babbey: None. K.L. March: None.
- © 2015 by American Heart Association, Inc.