Tracheobronchial innervation is deficient in infants and rats with congenital diaphragmatic hernia and it is rescued by retinoic acid and amniotic fluid stem cells

摘要: Congenital diaphragmatic hernia (CDH) still causes high mortality in newborns because of severe respiratory failure secondary to pulmonary hypoplasia. In addition, the ensuing chronic disease continues be most significant source morbidity survivors. Pulmonary hypoplasia and lung injury caused by mechanical ventilation have been recognized as major determinants morbidity. However, symptoms are also experienced patients with mild moderate hypoplasia, suggesting that other might involved. Autonomic nerves control tracheobronchial smooth muscle whose contractility modulates growth regulates airway patency. We therefore hypothesized impaired trachebronchial innervation interfere development contribute induce long-term bronchopulmonary symptoms. Using nitrofen experimental rat model CDH, we studied were able demonstrate it was deficient embryos fetuses CDH. investigated innervation, pointing out delayed CDH neural deficiency partially compensated an increase supporting glial tissue. attempt translate these findings human condition a partial explanation for survivors, looked same lesions infants could confirm their presence. We then undertook prenatal interventions improve above-mentioned deficiencies demonstrated cultured hypoplastic lungs both bronchial poor peristalsis rescued addition retinoic acid. Finally, explored vitro, explants, vivo, using intra-amniotic injection, possible beneficial effects amniotic fluid stem cells on viability this approach.