Late Rescue Therapy with Cord-Derived Mesenchymal Stromal Cells for Established Lung Injury in Experimental Bronchopulmonary Dysplasia

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Megan O'Reilly - , University of Alberta (Author)
  • Marius A Möbius - , Department of Paediatrics, University of Alberta, Women and Children's Health Research Institute (Author)
  • Arul Vadivel - , University of Ottawa (Author)
  • Lavinia Ionescu - , University of Alberta (Author)
  • Moses Fung - , University of Alberta (Author)
  • Farah Eaton - , University of Alberta (Author)
  • John J Greer - , University of Alberta (Author)
  • Bernard Thébaud - , University of Ottawa (Author)

Abstract

Bronchopulmonary dysplasia (BPD), the main complication of extreme prematurity, has lifelong consequences for lung health. Mesenchymal stromal cells (MSCs) prevent lung injury in experimental BPD in newborn rodents when given in the immediate neonatal period. Whether MSC therapy can restore normal lung growth after established lung injury in adulthood is clinically relevant, but currently unknown. Experimental BPD was achieved by exposing newborn rats to 95% O 2 from postnatal days 4-14. Human umbilical cord-derived MSCs were intratracheally administered to rats (1 × 10 6cells/kg body weight) as a single dose at 3 or 6 months of age followed by assessment at 5 or 8 months of age, respectively. Lung alveolar structure and vessel density were histologically analyzed. O 2-exposed rats exhibited persistent lung injury characterized by arrested alveolar growth with airspace enlargement and a lower vessel density at both 5 and 8 months of age compared with controls. Single-dose MSC treatment at 3 months partially attenuated O 2-induced alveolar injury and restored vessel density at 5 months. Treatment with a single dose at 6 months did not attenuate alveolar injury or vessel density at 8 months. However, treatment with multiple MSC doses at 6, 6.5, 7, and 7.5 months significantly attenuated alveolar injury and improved vessel density at 8 months of age. Treatment of the adult BPD lung with MSCs has the potential to improve lung injury if administered in multiple doses or at an early stage of adulthood.

Details

Original languageEnglish
Pages (from-to)364-371
Number of pages8
JournalStem cells and development
Volume29
Issue number6
Publication statusPublished - 15 Mar 2020
Peer-reviewedYes

External IDs

Scopus 85082092765

Keywords

Sustainable Development Goals

Keywords

  • Age Factors, Animals, Animals, Newborn, Bronchopulmonary Dysplasia/complications, Cells, Cultured, Disease Models, Animal, Humans, Hyperoxia/physiopathology, Lung Injury/etiology, Mesenchymal Stem Cell Transplantation/methods, Mesenchymal Stem Cells/cytology, Rats, Sprague-Dawley, Transplantation, Heterologous, Wharton Jelly/cytology