The Effects of Bone Marrow-Derived Mesenchymal Stem Cells on Alveolarization Inhibition Induced by Hyperoxia in Neonatal Rat

ABSTRACT

PURPOSE: We sought to determine whether bone marrow-derived mesenchymal stem cells (BMMSC) could attenuate the inhibition of alveolarization induced by hyperoxia. METHODS: Human BMMSC (SNU-hMSC) were infused into the peritoneal cavity (IP) or trachea (IT) of neonatal rats exposed to hyperoxia (90% O2 from D1) on D5. The rats were then exposed to the same degree of hyperoxia for another 9d and sacrificed on D21. Morphometric analysis of the lungs and immunofluorescent staining in order to determine cell fates of infused SNU-hMSC were performed. RESULTS: The airspace of the hyperoxia control group (90% O2 for 14d) was significantly larger and more simple (mean linear intercept [Lm] 68+/-16 micrometer vs 33+/-3 micrometer) and the alveolar surface area [SA] was significantly smaller (646+/-72 cm2 vs 1,042+/-477 cm2) than those of the normoxia control group. The Lm of the BMMSC- infused groups was significantly shorter irrespective of infusion route (52+/-2 micrometer [IP], 50+/-8 micrometer [IT] vs 68+/-16 micrometer) and the SA of the BMMSC IP infusion group was significantly larger (646+/-172 cm2 vs 346+/-142 cm2) than those of the hyperoxia control group. The IT-, but not IP-, infused BMMSC groups were observed in lung tissue and assumed to be type I and type II alveolar epithelial cell phenotypes. CONCLUSION: BMMSC, when infused into neonatal rats exposed to hyperoxia, significantly attenuated the inhibition of alveolarization irrespective of the infusion route. It seems that BMMSC, when infused IT, engrafts into lung tissue and differentiates into alveolar epithelial cells. These results indicate that BMMSC could be considered as a potential candidate therapy for bronchopulmonary dysplasia.