Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 181, Issue 5, Pages 1681-1692Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2012.08.009
Keywords
-
Categories
Funding
- Canadian Institutes of Health Research [MOP-106545, MOP-74752]
- Ontario Thoracic Society [OTS2010/2011/2012]
- Physicians Services Incorporate [PSI 09-21]
- Northern Therapeutics
- Natural Sciences and Engineering Research Council of Canada Doctoral Canada Graduate Scholarship
- Ontario Graduate Scholarship
- Weston Foundation
- McLaughlin Center for Molecular Medicine
- Canada Research Chair in Infectious Diseases and Inflammation
Ask authors/readers for more resources
Although bone marrow derived mesenchymal stem cell (MSC) systemic administration reduces sepsis-associated inflammation, organ injury, and mortality in clinically relevant models of polymicrobial sepsis, the cellular and molecular mechanisms mediating beneficial effects are controversial. This study identifies the molecular mechanisms of MSC-conferred protection in sepsis by interrogating transcriptional responses of target organs to MSC therapy. Sepsis was induced in C57B1/6J mice by cecal ligation and puncture, followed 6 hours later by an i.v. injection of either MSCs or saline. Total RNA from lungs, hearts, kidneys, livers, and spleens harvested 28 hours after cecal ligation and puncture was hybridized to mouse expression bead arrays. Common transcriptional responses were analyzed using a network knowledge-based approach. A total of 4751 genes were significantly changed between placebo- and MSC-treated mice (adjusted P <= 0.05). Transcriptional responses identified three common effects of MSC administration in all five organs examined: i) attenuation of sepsis-induced mitochondrial-related functional derangement, ii down-regulation of endotoxin/Toll-like receptor innate immune proinflammatory transcriptional responses, and iii) coordinated expression of transcriptional programs implicated in the preservation of endothelial/vascular integrity. Transcriptomic analysis indicates that the protective effect of MSC therapy in sepsis is not limited to a single mediator or pathway but involves a range of complementary activities affecting biological networks playing critical roles in the control of host cell metabolism and inflammatory response. (Am J Pathol 2012, 181:1681-1692; http://dx.doi.org/10.1016/j.ajpath.2012.08.009)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available