Fellows of the Lovelace Respiratory Research Institute, Albuquerque, New Mexico
Translational and Clinical Research
Article first published online: 12 FEB 2013
Copyright © 2012 AlphaMed Press
Volume 31, Issue 2, pages 397–407, February 2013
How to Cite
Hall, S. R. R., Tsoyi, K., Ith, B., Padera, R. F., Lederer, J. A., Wang, Z., Liu, X. and Perrella, M. A. (2013), Mesenchymal Stromal Cells Improve Survival During Sepsis in the Absence of Heme Oxygenase-1: The Importance of Neutrophils. STEM CELLS, 31: 397–407. doi: 10.1002/stem.1270
Author contributions: S.R.R.H.: conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing; K.T. and X.L.: conception and design, collection and/or assembly of data, and data analysis and interpretation; B.I. and Z.W.: collection and/or assembly of data; R.F.P.: data analysis and interpretation; J.A.L.: conception and design and data analysis and interpretation; M.A.P.: conception and design, financial and administrative support, data analysis and interpretation, manuscript writing, and final approval of manuscript.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSEXPRESS November 6, 2012.
- Issue published online: 12 FEB 2013
- Article first published online: 12 FEB 2013
- Accepted manuscript online: 6 NOV 2012 11:34PM EST
- Manuscript Accepted: 1 OCT 2012
- Manuscript Revised: 8 SEP 2012
- Manuscript Received: 5 MAY 2012
- National Institutes of Health Grants. Grant Numbers: RO1HL060788, PO1HL108801-01 (Project 3), LRRI-BWH
- Lovelace Respiratory Research Institute
- Polymicrobial sepsis;
- Mesenchymal stromal cells;
- Compact bone;
- Bacterial clearance;
The use of mesenchymal stromal cells (MSCs) for treatment of bacterial infections, including systemic processes like sepsis, is an evolving field of investigation. This study was designed to investigate the potential use of MSCs, harvested from compact bone, and their interactions with the innate immune system, during polymicrobial sepsis induced by cecal ligation and puncture (CLP). We also wanted to elucidate the role of endogenous heme oxygenase (HO)-1 in MSCs during a systemic bacterial infection. MSCs harvested from the bones of HO-1 deficient (−/−) and wild-type (+/+) mice improved the survival of HO-1−/− and HO-1+/+ recipient mice when administered after the onset of polymicrobial sepsis induced by CLP, compared with the administration of fibroblast control cells. The MSCs, originating from compact bone in mice, enhanced the ability of neutrophils to phagocytize bacteria in vitro and in vivo and to promote bacterial clearance in the peritoneum and blood after CLP. Moreover, after depleting neutrophils in recipient mice, the beneficial effects of MSCs were entirely lost, demonstrating the importance of neutrophils for this MSC response. MSCs also decreased multiple organ injury in susceptible HO-1−/− mice, when administered after the onset of sepsis. Taken together, these data demonstrate that the beneficial effects of treatment with MSCs after the onset of polymicrobial sepsis is not dependent on endogenous HO-1 expression, and that neutrophils are crucial for this therapeutic response. STEM CELLS2013;31:397–407