Development of a novel humanized mouse model to study bronchopulmonary dysplasia

Rationale The role of circulating fetal monocytes in bronchopulmonary dysplasia is not known. We utilized a humanized mouse model that supports human progenitor cell engraftment (MISTRG) to test the hypothesis prenatal monocyte programming alters early lung development and response hyperoxia. Methods Cord blood-derived from 10 infants were adoptively transferred into newborn MISTRG mice at p0 (1 × 6 cells/mouse, intrahepatic injection) followed by normoxia versus hyperoxia (85% oxygen 14 days). Lungs harvested p14 for alveolar histology (alveolar count, perimeter area) vascular parameters (vWF staining microvessel density, Fulton's index). Human CD45 was conducted compare presence hematopoietic cells. Murine compared among placebo monocyte-injected groups. individual profiles patients further considered, including gestational age (GA; n = 2 term, 3 moderate/late preterm, 5 very preterm infants) preeclampsia ( 4 patients). To explore microenvironment these patients, 30 cytokines/chemokines measured corresponding plasma multiplex immunoassay. Results Across majority mice, alveolarization simplified density decreased following Hyperoxia-induced changes seen both (PBS) mice. Under normoxic conditions, altered modestly as with P < 0.05). Monocyte injection associated increased P14 (26.7 ± 0.73 vs. 18.8 1.7 vessels per field; 0.001). Pooled analysis revealed births complicated lower GA vascularization under conditions. These differences modified CD45+ count positively correlated chemoattractant protein-1 0.001) macrophage inflammatory protein-1β 0.01). Immunohistochemical CD206 F4/80 confirmed absence macrophages lungs P14. Conclusions Despite inherent stages development, immunodeficient microvascular induced monocytes. exposed neonatal may serve novel study isolated effects on pulmonary development.