Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia
- Naveen Gupta1,
- Anna Krasnodembskaya2,
- Maria Kapetanaki1,
- Majd Mouded1,
- Xinping Tan1,
- Vladimir Serikov3,
- Michael A Matthay2
- 1Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
- 2Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California, USA
- 3Children's Hospital of Oakland Research Institute, Oakland, California, USA
- Correspondence to Assistant Professor Naveen Gupta, The Scripps Research Institute, MEM-180, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA; ngupta{at}scripps.edu
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Contributors NG: conception and design, financial support, collection and/or assembly of data, data analysis and interpretation, manuscript writing; AK: conception and design, collection and/or assembly of data, data analysis and interpretation, manuscript writing; MK: collection and/or assembly of data, data analysis and interpretation, manuscript writing; MM: data analysis and interpretation, manuscript writing; XT: collection and/or assembly of data, data analysis and interpretation; VS: conception and design, data analysis and interpretation; MAM: conception and design, financial support, data analysis and interpretation, manuscript writing.
- Received 29 September 2011
- Accepted 15 December 2011
- Published Online First 16 January 2012
Abstract
Rationale Bacterial pneumonia is the most common infectious cause of death worldwide and treatment is increasingly hampered by antibiotic resistance. Mesenchymal stem cells (MSCs) have been demonstrated to provide protection against acute inflammatory lung injury; however, their potential therapeutic role in the setting of bacterial pneumonia has not been well studied.
Objective This study focused on testing the therapeutic and mechanistic effects of MSCs in a mouse model of Gram-negative pneumonia.
Methods and results Syngeneic MSCs from wild-type mice were isolated and administered via the intratracheal route to mice 4 h after the mice were infected with Escherichia coli. 3T3 fibroblasts and phosphate-buffered saline (PBS) were used as controls for all in vivo experiments. Survival, lung injury, bacterial counts and indices of inflammation were measured in each treatment group. Treatment with wild-type MSCs improved 48 h survival (MSC, 55%; 3T3, 8%; PBS, 0%; p<0.05 for MSC vs 3T3 and PBS groups) and lung injury compared with control mice. In addition, wild-type MSCs enhanced bacterial clearance from the alveolar space as early as 4 h after administration, an effect that was not observed with the other treatment groups. The antibacterial effect with MSCs was due, in part, to their upregulation of the antibacterial protein lipocalin 2.
Conclusions Treatment with MSCs enhanced survival and bacterial clearance in a mouse model of Gram-negative pneumonia. The bacterial clearance effect was due, in part, to the upregulation of lipocalin 2 production by MSCs.
Footnotes
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See Editorial, p 475
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NG and AK contributed equally to this work.
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Funding This work was supported by the following institutions and grants: NHLBI HL092059 (NG), Parker B Francis Foundation Pulmonary Fellowship (NG) and NHLBI 51856, 51854 (MAM).
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Competing interests None.
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Provenance and peer review Not commissioned; externally peer reviewed.
