Paracrine Effect of Mesenchymal Stromal Cells on Multifactorial Lung Injury in Neonatal Mice

  • Author / Creator
    Strueby, Lannae L.
  • Bronchopulmonary dysplasia (BPD) is a common complication of extreme prematurity. Preterm infants often require mechanical ventilation and supplemental oxygen for survival. These interventions increase the risk of developing BPD. Despite its frequency, there remains no effective treatment for BPD. Evidence suggests that mesenchymal stromal cells (MSCs) prevent oxygen-induced lung injury in rodent models of BPD. The benefits observed appear mediated via paracrine effects. We explored the ability of cell-free conditioned media (CDM) from human umbilical cord-derived MSCs (MSC-CDM) to prevent lung damage in a neonatal mouse model of BPD combining inflammation, ventilation-induced lung injury, and supplemental oxygen. Neonatal mice (C57BL/6) were mechanically ventilated at postnatal day 9-10 for 8 hours with a tidal volume of 10µl/g, 180 breaths/minute and 40% oxygen. Inflammation was induced by intraperitoneal administration of lipopolysaccharide (LPS) 48 hours preceding ventilation. Age matched unventilated mice that did not receive LPS were used as controls. The treatment group received intratracheal MSC-CDM (3µl/g) immediately prior to mechanical ventilation. At completion of ventilation lungs were harvested for structural and molecular analysis. Ventilated mice that received LPS exhibited alveolar simplification and reduced vascular density compared to controls as demonstrated by a significantly greater mean linear intercept and reduced number of vessels per high power field (p<0.05). These mice also exhibited elevated levels of macrophage inflammatory protein – 2 (MIP-2) and monocyte chemoattractant protein – 2 (MCP-1) compared with controls (p<0.05). Intratracheal MSC-CDM treatment significantly attenuated structural lung injury and improved vascular density compared with untreated, ventilated mice (p<0.05), but did not significantly reduce levels of MIP-2/MCP-1. Treatment with MSC-CDM attenuates structural lung injury and improves vessel density in a clinically relevant neonatal mouse model of BPD. By harnessing the beneficial effects of MSC-CDM, new therapies for treating BPD may be developed.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Physiology
  • Supervisor / co-supervisor and their department(s)
    • Greer, John (Physiology)
    • Thébaud, Bernard (Physiology)
  • Examining committee members and their departments
    • Thébaud, Bernard (Physiology)
    • Alexander, Todd (Physiology)
    • MacLean, Joanna (Pediatrics)
    • Greer, John (Physiology)