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Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes

Academic Article
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Overview

authors

  • Krasnodembskaya, A.
  • Samarani, G.
  • Song, Y. L.
  • Zhuo, H. J.
  • Su, X.
  • Lee, Jiing-Dwan
  • Gupta, Naveen
  • Petrini, M.
  • Matthay, M. A.

publication date

  • May 2012

journal

  • American Journal of Physiology-Lung Cellular and Molecular Physiology  Journal

abstract

  • The potential therapeutic value of cell-based therapy with mesenchymal stem cells (MSC) has been reported in mouse models of polymicrobial peritoneal sepsis. However, the mechanisms responsible for the beneficial effects of MSC have not been well defined. Therefore, we tested the therapeutic effect of intravenous bone marrow-derived human MSC in peritoneal sepsis induced by gram-negative bacteria. At 48 h, survival was significantly increased in mice treated with intravenous MSC compared with control mice treated with intravenous fibroblasts (3T3) or intravenous PBS. There were no significant differences in the levels of TNF-α, macrophage inflammatory protein 2, or IL-10 in the plasma. However, there was a marked reduction in the number of bacterial colony-forming units of Pseudomonas aeruginosa in the blood of MSC-treated mice compared with the 3T3 and PBS control groups. In addition, phagocytic activity was increased in blood monocytes isolated from mice treated with MSC compared with the 3T3 and PBS groups. Furthermore, levels of C5a anaphylotoxin were elevated in the blood of mice treated with MSC, a finding that was associated with upregulation of the phagocytosis receptor CD11b on monocytes. The phagocytic activity of neutrophils was not different among the groups. There was also an increase in alternately activated monocytes/macrophages (CD163- and CD206-positive) in the spleen of the MSC-treated mice compared with the two controls. Thus intravenous MSC increased survival from gram-negative peritoneal sepsis, in part by a monocyte-dependent increase in bacterial phagocytosis.

subject areas

  • Animals
  • Antigens, CD
  • Bacteremia
  • Colony Count, Microbial
  • Cytokines
  • Disease Models, Animal
  • Fibroblasts
  • Humans
  • Injections, Intravenous
  • Macrophages
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells
  • Mice
  • Mice, Inbred C57BL
  • Monocytes
  • Phagocytosis
  • Pseudomonas aeruginosa
  • Sepsis
  • Survival Rate
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Research

keywords

  • Pseudomonas aeruginosa
  • monocytes
  • peritonitis
  • phagocytosis
  • platelets
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Identity

PubMed Central ID

  • PMC3362255

International Standard Serial Number (ISSN)

  • 1040-0605

Digital Object Identifier (DOI)

  • 10.1152/ajplung.00180.2011

PubMed ID

  • 22427530
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Additional Document Info

start page

  • L1003

end page

  • L1013

volume

  • 302

issue

  • 10

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