Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice

Respir Res. 2011 Aug 15;12(1):108. doi: 10.1186/1465-9921-12-108.

Abstract

Background: Human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) attenuate hyperoxic neonatal lung injury primarily through anti-inflammatory effects. We hypothesized that intratracheal transplantation of human UCB-derived MSCs could attenuate Escherichia coli (E. coli)-induced acute lung injury (ALI) in mice by suppressing the inflammatory response.

Methods: Eight-week-old male ICR mice were randomized to control or ALI groups. ALI was induced by intratracheal E. coli instillation. Three-hours after E. coli instillation, MSCs, fibroblasts or phosphate-buffered saline were intratracheally administered randomly and survival was analyzed for 7 days post-injury. Lung histology including injury scores, myeloperoxidase (MPO) activity, and protein levels of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein (MIP)-2 as well as the wet-dry lung ratio and bacterial counts from blood and bronchoalveolar lavage (BAL) were evaluated at 1, 3, and 7 days post-injury. Levels of inflammatory cytokines in the lung were also profiled using protein macroarrays at day 3 post-injury which showed peak inflammation.

Results: MSC transplantation increased survival and attenuated lung injuries in ALI mice, as evidenced by decreased injury scores on day 3 post-injury and reduced lung inflammation including increased MPO activity and protein levels of IL-1α, IL-1β, IL-6, TNF-α, and MIP-2 on day 3 and 7 post-injury. Inflammatory cytokine profiles in the lungs at day 3 post-injury were attenuated by MSC transplantation. MSCs also reduced the elevated lung water content at day 3 post-injury and bacterial counts in blood and BAL on day 7 post-injury.

Conclusions: Intratracheal transplantation of UCB-derived MSCs attenuates E. coli-induced ALI primarily by down-modulating the inflammatory process and enhancing bacterial clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / immunology
  • Acute Lung Injury / microbiology
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control*
  • Animals
  • Chemokine CXCL2 / metabolism
  • Cord Blood Stem Cell Transplantation*
  • Disease Models, Animal
  • Escherichia coli / pathogenicity*
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-1alpha / metabolism
  • Interleukin-1beta / metabolism
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Lung / surgery*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Peroxidase / metabolism
  • Pneumonia, Bacterial / immunology
  • Pneumonia, Bacterial / microbiology
  • Pneumonia, Bacterial / pathology
  • Pneumonia, Bacterial / surgery*
  • Protein Array Analysis
  • Pulmonary Edema / microbiology
  • Pulmonary Edema / prevention & control
  • Severity of Illness Index
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Inflammation Mediators
  • Interleukin-1alpha
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Peroxidase