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Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat.

James Devaney1, Shahd Horie1, Claire Masterson1

  • 1Department of Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway, Ireland Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.

Thorax
|May 20, 2015
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Summary

Human mesenchymal stromal cells (hMSCs) effectively treat E. coli pneumonia in rats, improving survival and reducing lung injury. Therapy enhances macrophage function and boosts antimicrobial peptide LL-37 levels.

Keywords:
ARDSBacterial Infection

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Area of Science:

  • Regenerative Medicine
  • Immunology
  • Infectious Disease

Background:

  • Mesenchymal stromal cells (MSCs) show promise for acute respiratory distress syndrome.
  • The efficacy of human MSCs (hMSCs) in treating prolonged bacterial pneumonia-induced lung injury requires further investigation.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of hMSCs in a rat model of acute lung injury from Escherichia coli pneumonia.
  • To elucidate the mechanisms underlying hMSC treatment, including effects on bacterial load, inflammation, and host defense.

Main Methods:

  • Rats with E. coli-induced pneumonia received intravenous or intratracheal administration of vehicle, fibroblasts, or varying doses of hMSCs.
  • Studies also assessed cryopreserved hMSCs, the hMSC secretome, and in vitro hMSC-macrophage interactions.
  • Key outcomes included survival, lung injury scores, bacterial burden, inflammatory markers, macrophage phagocytosis, and LL-37 levels.

Main Results:

  • hMSC therapy significantly improved survival, reduced lung injury, and decreased bacterial load in rats with E. coli pneumonia.
  • Effective therapeutic doses were as low as 5x10^6 hMSCs/kg, with intratracheal administration being as effective as intravenous.
  • hMSC treatment enhanced macrophage phagocytosis and increased concentrations of the antimicrobial peptide LL-37 in the lungs and systemically.

Conclusions:

  • hMSC therapy is a promising treatment for E. coli-induced pneumonia, ameliorating lung injury and bacterial burden.
  • Therapeutic effects are potentially mediated by enhanced macrophage phagocytic capacity and increased alveolar LL-37 concentrations.