Treatment of neonatal mouse hyperoxia-induced lung deficit with endothelial progenitor cells from bone marrow

Alexandra Firsova
Premature birth-related lung deficit caused by high oxygen treatment (hyperoxia) can result in chronic lung disease. Previous studies demonstrated that disruption of alveolarisation (septation of the lung) and pulmonary vascularisation can be observed after hyperoxia. Injection of cultured cells isolated from bone marrow with mesenchymal or endothelial progenitor phenotype can return lung morphology to normal after neonatal hyperoxia in mice. However, long-term efficiency, as well as any
more » ... well as any potential side effects of such cell therapies, remains under investigation. In this study we hypothesised that endothelial progenitor cells and plate-adherent cells can be isolated from bone marrow, and can be used for treating the effects of hyperoxia in the lungs of neonatal mice by inducing or supporting alveolarisation via promotion of vascularisation. The aim of this project was to compare a number of endothelial progenitor cell types, first in vitro, and then in vivo, to determine how injection of various cell types from mouse bone marrow affects the hyperoxia-treated and healthy lung, which would result in the optimisation of a new treatment model. Newborn mice were treated with 90% oxygen or left in room air for four days. Samples of tissues were collected from hyperoxia-treated and normoxia mice at 5, 28 and 56 days postpartum. It was discovered that alveolarisation remains affected until 56 days of age, but vascularisation recovers by 28 days of age. Suitable cell types were then obtained in order to treat the effects of hyperoxia. Cell sorting of bone marrow, in vitro differentiation and analysis for the presence of vessel-like structures revealed that the freshly-isolated Kdr-enriched cell fraction is effective in forming blood-vessel-like structures in vitro and might have in vivo potential. EphA3-enriched cells from different passages were also selected based on relatively rapid vessel-like structure formation in vitro, and unsorted plate-adherent cells from passage 0 were used as a control. Hyperoxia-treated and no [...]
doi:10.4225/03/58980e97a4b00 fatcat:equlxqp3bffctjd2frxbjwlbo4