title: Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. ngupta@scripps.edu
authors.forename: Naveen
authors.initials: N
authors.lastname: Gupta
authors.forename: Anna
authors.initials: A
authors.lastname: Krasnodembskaya
authors.forename: Maria
authors.initials: M
authors.lastname: Kapetanaki
authors.forename: Majd
authors.initials: M
authors.lastname: Mouded
authors.forename: Xinping
authors.initials: X
authors.lastname: Tan
authors.forename: Vladimir
authors.initials: V
authors.lastname: Serikov
authors.forename: Michael A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000150:complications* / Q000601:surgery*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis / Q000378:metabolism*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000378:metabolism*; D018410:Pneumonia, Bacterial / Q000382:microbiology* / Q000601:surgery; D016019:Survival Analysis; D014132:Trachea; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; C071332:Lcn2 protein, mouse