Abstract 16936: Mesenchymal Stem Cell Administration Attenuates Thoracic Aortic Aneurysm Formation
Introduction: Thoracic aortic aneurysms (TAA) are characterized by inflammation, cytokine upregulation, macrophage activation and matrix degradation. Mesenchymal stem cells (MSCs) have immunomodulatory characteristics that are known to inhibit murine abdominal aortic aneurysm formation.
Hypothesis: We hypothesize that MSC administration will attenuate aneurysm formation in the thoracic aorta.
Methods: Wild-type mice (C57BL/6; age 8-12 weeks) underwent thoracotomy and application of topical elastase to the descending thoracic aorta (n=5-14/group) using a previously established model of TAA. All mice underwent tail vein injections on postoperative days 1 and 5 with either 1 million human umbilical cord-derived MSCs or control (phosphate buffer saline). On postoperative day 14, the aortic diameter was measured and blood and tissue were harvested. Cytokine array was performed on pooled homogenized aortas while immunohistochemistry evaluated cellular infiltration and elastin fiber disruption. Statistical comparisons were performed using nonparametric univariate analysis.
Results: MSC treated mice demonstrated significantly decreased aortic diameter on postoperative day 14 compared to elastase controls (78.5% vs 102.2%, respectively; p=0.003; n=14/group). MSC treatment resulted in attenuation of cytokines, particularly IL-1α, IL-1ra, complement C5a, CXCL9, CXCL10, CCL2, TIMP-1, and Sicam-1 (all p=0.030). Histology demonstrated significantly less neutrophil and macrophage infiltration (both p=0. 036), as well as elastin degradation (p=0.042) in MSC- treated aortas.
Conclusions: MSC administration significantly attenuates descending thoracic aortic aneurysm dilation in a topical elastase murine model. Aortic tissue demonstrates decreased inflammatory cytokines, complement levels, leukocyte infiltration and elastin degradation. These results signify that MSCs can be a viable option for the mitigation of TAAs.
Author Disclosures: R.B. Hawkins: None. M. Salmon: None. G. Su: None. A. Fashandi: None. M. Spinosa: None. G. Unchurch: None. A. Sharma: None. G. Ailawadi: None.
- © 2016 by American Heart Association, Inc.