Experimental BPD – cells from human umbilical cord blood improve lung development in a double-hit mouse model

Abstract

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease in neonates with low gestational age and low birth weight. Besides the consequences for the neonatal period, the disease also affects the further development of the patients with lifelong consequences like persistent lung abnormalities. BPD has a multifactorial etiology with main risk factors being prematurity, low birth weight, oxygen therapy or infection. Among other symptoms, “new” BPD often presents with alveolar arrest and impaired lung development. Several studies showed improvement of lung development in rodent models using stem cells of different origin. Objectives: To investigate the effects of human umbilical cord blood cells (buffy coat), including progenitor and stem cells on the lung development in a BPD double-hit model. Methods: We established a new double-hit animal model in the mouse, combining prenatal hypoxia (4 days) and postnatal hyperoxia (13 days), thus combining lung damage with low birth weight to get closer to the multifactorial situation in humans. The mice were intraperitoneally injected with cells from human umbilical cord blood at postnatal day seven. The mRNA expression in lung tissue was analysed for SPB, SPC, VEGF, Elastin, HIF1a, mTOR, IGF1, RARα, RARβ, RARγ, CRABP1, RBP1, TGFb1, TGFb2, TGFb3. Results: The double-hit mice were smaller at birth than normal mice and developed more slowly. The lung structure in the double-hit mice was less developed compared to normal mice. Septal surface was decreased and septa were thickened. Treatment with buffy coat cells resulted in a tendency towards better growth of the pups. Lung structure was improved compared to untreated mice. Furthermore there was a tendency to a changed expression of several genes, being the most clear for mTOR. Conclusions: Treatment with human umbilical cord blood cells has an overall positive effect on growth and development in general and lung development in particular in our double-hit mouse model for BPD. Further studies are necessary in order to further improve stem cell therapy in experimental BPD.