title: Long-term reparative effects of mesenchymal stem cell therapy following neonatal hyperoxia-induced lung injury.
abstract: BACKGROUND
  Mesenchymal stem cell (MSC) therapy may prevent neonatal hyperoxia-induced lung injury (HILI). There are, however, no clear data on the therapeutic efficacy of MSC therapy in established HILI, the duration of the reparative effects, and the exact mechanisms of repair. The main objective of this study was to evaluate whether the long-term reparative effects of a single intratracheal (IT) dose of MSCs or MSC-conditioned medium (CM) are comparable in established HILI.
  
  
  METHODS
  Newborn rats exposed to normoxia or hyperoxia from postnatal day (P)2)-P16 were randomized to receive IT MSCs, IT CM, or IT placebo (PL) on P9. Alveolarization and angiogenesis were evaluated at P16, P30, and P100.
  
  
  RESULTS
  At all time periods, there were marked improvements in alveolar and vascular development in hyperoxic pups treated with MSCs or CM as compared with PL. This was associated with decreased expression of inflammatory mediators and an upregulation of angiogenic factors. Of note, at P100, the improvements were more substantial with MSCs as compared with CM.
  
  
  CONCLUSIONS
  These data suggest that acute effects of MSC therapy in HILI are mainly paracrine mediated; however, optimum long-term improvement following HILI requires treatment with the MSCs themselves or potentially repetitive administration of CM.
authors.affiliation: Department of Pediatrics/Division of Neonatology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Sutsko
authors.forename: Karen C
authors.initials: KC
authors.lastname: Young
authors.forename: Ana
authors.initials: A
authors.lastname: Ribeiro
authors.forename: Eneida
authors.initials: E
authors.lastname: Torres
authors.forename: Myra
authors.initials: M
authors.lastname: Rodriguez
authors.forename: Dorothy
authors.initials: D
authors.lastname: Hehre
authors.forename: Carlos
authors.initials: C
authors.lastname: Devia
authors.forename: Ian
authors.initials: I
authors.lastname: McNiece
authors.forename: Cleide
authors.initials: C
authors.lastname: Suguihara
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D005260:Female; D018496:Hyperoxia / Q000150:complications*; D017380:Hypertrophy, Right Ventricular / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000628:therapy*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017077:Culture Media, Conditioned