Attenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation

• Type of Material: Article
• Authors: Daniel A. Grove, Emory University; Jianguo Xu, Emory University; Robert Joodi, Emory University; Edilson Torres-Gonzales, Emory University; David Neujahr, Emory University; Ana L. Mora, University of Pittsburgh; Mauricio Rojas, University of Pittsburgh
• Language: English
• Date: 2011-03-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 International Society for Heart and Lung Transplantation. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.healun.2010.09.012
• Title of Journal or Parent Work: Journal of Heart and Lung Transplantation
• ISSN: 1053-2498
• Volume: 30
• Issue: 3
• Start Page: 341
• End Page: 350
• Grant/Funding Information: This research was supported by grant number 5K01HL084683-02 from the National Heart Lung and Blood Institute, a grant from the American Federation for Aging Research, Emory University URC #2003100 and the McKelvey Center for Lung Transplantation at Emory University.
• Keywords: Life Sciences & Biomedicine; OBLITERATIVE BRONCHIOLITIS; Science & Technology; airway obstruction; therapy; Surgery; Cardiovascular System & Cardiology; BONE-MARROW; INJURY; mesenchymal stem cells; MICE; LUNG-TRANSPLANTATION; Cardiac & Cardiovascular Systems; Respiratory System; Transplantation; ENGRAFTMENT; DISEASE
• Research Categories: Biology, General

Abstract

Background Long-term success in lung transplantation is limited by obliterative bronchiolitis (OB). Presently, complete understanding of the mechanisms of OB has been elusive. Bone marrowderived mesenchymal stem cells (MSC) have been shown to modulate repair of the injured lung in multiple disease models. We hypothesized that the injection of MSC would prevent development of early airway obstruction (AO) in the heterotopic tracheal transplant model. Methods Forty-four tracheas from BALB/c and C57BL/6 donors were transplanted into 22 C57BL/6 recipients. At the time of transplant, 13 of the allogeneic recipient mice were injected with 5 × 105 MSC from various murine sources. To confirm the role of the immune response in the generation of AO we used a permeable inhibitor of nuclear factor-kappaB (NF-κB) in 11 recipients after transplantation with 22 BALB/c tracheas. Results After transplantation, administration of MSC inhibited intraluminal obstruction by collagen in 98% of the mice and transforming factor-beta (TGF-β) expression decreased to levels similar to those observed in isograft controls. These effects were associated with a significant (p < 0.05) increase in expression of the anti-inflammatory cytokine interleukin-10 (IL-10). NF-κB inhibitor showed decreased expression of transforming growth factor-beta (TGF-β) in the Day 7 and Day 14 groups, resulting in a 60% reduction of luminal obstruction as well as a decrease in inflammatory cells to the airway. Conclusion Our observations suggest that administration of MSC prevents development of airway occlusion in a mouse model, probably through the modulated immune response altering TGF-β expression.