title: Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia.
abstract: BACKGROUND
  Bronchopulmonary dysplasia (BPD) remains a main complication of extreme prematurity and currently lacks efficient treatment. Rat bone marrow-derived mesenchymal stem cells (MSC) prevent lung injury in an oxygen-induced model of BPD. Human cord is an advantageous source of stem cells that is especially appealing for the treatment of neonatal diseases. The therapeutic benefit after established lung injury and long-term safety of cord-derived stem cells is unknown.
  
  
  METHODS
  Human cord-derived perivascular cells (PCs) or cord blood-derived MSCs were delivered prophylactically or after established alveolar injury into the airways of newborn rats exposed to hyperoxia, a well-established BPD model.
  
  
  RESULTS
  Rat pups exposed to hyperoxia showed the characteristic arrest in alveolar growth with air space enlargement and loss of lung capillaries. PCs and MSCs partially prevented and rescued lung function and structure. Despite therapeutic benefit, cell engraftment was low, suggesting that PCs and MSCs act via a paracrine effect. Accordingly, cell free-derived conditioned media from PCs and MSCs also exerted therapeutic benefit when used either prophylactically or therapeutically. Finally, long-term (6 months) assessment of stem cell or conditioned media therapy showed no adverse lung effects of either strategy, with persistent improvement in exercise capacity and lung structure.
  
  
  CONCLUSIONS
  Human umbilical cord-derived PCs and MSCs exert short- and long-term therapeutic benefit without adverse lung effects in this experimental model and offer new therapeutic options for lung diseases characterised by alveolar damage.
authors.affiliation: Department of Pediatrics, Cardiovascular Research Center and Pulmonary Research Group, School of Human Development, Women and Children's Health Research Institute, University of Alberta, Edmonton, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: Pierro
authors.forename: Lavinia
authors.initials: L
authors.lastname: Ionescu
authors.forename: Tiziana
authors.initials: T
authors.lastname: Montemurro
authors.forename: Arul
authors.initials: A
authors.lastname: Vadivel
authors.forename: Gaia
authors.initials: G
authors.lastname: Weissmann
authors.forename: Gavin
authors.initials: G
authors.lastname: Oudit
authors.forename: Derek
authors.initials: D
authors.lastname: Emery
authors.forename: Sreedhar
authors.initials: S
authors.lastname: Bodiga
authors.forename: Farah
authors.initials: F
authors.lastname: Eaton
authors.forename: Bruno
authors.initials: B
authors.lastname: Péault
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.forename: Lorenza
authors.initials: L
authors.lastname: Lazzari
authors.forename: Bernard
authors.initials: B
authors.lastname: Thébaud
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D000831:Animals, Newborn; D001997:Bronchopulmonary Dysplasia / Q000150:complications / Q000473:pathology / Q000601:surgery*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004195:Disease Models, Animal; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019899:Paracrine Communication; D051381:Rats; D012129:Respiratory Function Tests; D014470:Umbilical Cord / Q000166:cytology*
chemical_list: D017077:Culture Media, Conditioned