Intratracheal transplantation of mesenchymal stem cells simultaneously attenuates both lung and brain injuries in hyperoxic newborn rats.

ABSTRACT

BACKGROUND: Bronchopulmonary dysplasia is an independent risk factor for adverse neurodevelopmental outcomes in premature infants. We investigated whether attenuation of hyperoxic lung injury with intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells (MSCs) could simultaneously mitigate brain damage in neonatal rats. METHODS: Newborn Sprague-Dawley rats were exposed to hyperoxia or normoxia conditions for 14 d. MSCs (5 × 10(5) cells) were transplanted intratracheally at postnatal day (P) 5. At P14, lungs and brains were harvested for histological and biochemical analyses. RESULTS: Hyperoxic lung injuries, such as impaired alveolarization evident from increased mean linear intercept (MLI) and elevated inflammatory cytokine levels were significantly alleviated with MSC transplantation. Hyperoxia decreased brain weight, increased brain cell death, and induced hypomyelination. MSC transplantation significantly ameliorated hyperoxia-induced increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells in the dentate gyrus and reduced myelin basic protein. In correlation analyses, brain weight and myelin basic protein (MBP) were significantly inversely correlated with lung MLI and inflammatory cytokines, while TUNEL-positive brain cell number showed a significant positive correlation with lung MLI. CONCLUSION: Despite no significant improvement in short-term neurofunctional outcome, intratracheal transplantation of MSCs simultaneously attenuated hyperoxic lung and brain injuries in neonatal rats, with the extent of such attenuation being closely linked in the two tissues.