Stem cell therapy for neonatal diseases associated with preterm birth

In the last decades, the prevention and treatment of neonatal respiratory distress syndrome with antenatal steroids and surfactant replacement allowed the survival of infants born at extremely low gestational ages. These extremely preterm infants are highly vulnerable to the detrimental effects of oxidative stress and infection, and are prone to develop lung and brain diseases that eventually evolve in severe sequelae: The so-called new bronchopulmonary dysplasia (BPD) and the noncystic, diffuse form of periventricular leukomalacia (PVL). Tissue simplification and developmental arrest (larger and fewer alveoli and hypomyelination in the lungs and brain, respectively) appears to be the hallmark of these emerging sequelae, while fibrosis is usually mild and contributes to a lesser extent to their pathogenesis. New data suggest that loss of stem/progenitor cell populations in the developing brain and lungs may underlie tissue simplification. These observations constitute the basis for the application of stem cell-based protocols following extremely preterm birth. Transplantation of different cell types (including, but not limited to, mesenchymal stromal cells, endothelial progenitor cells, human amnion epithelial cells) could be beneficial in preterm infants for the prevention and/or treatment of BPD, PVL and other major sequelae of prematurity. However, before this new knowledge can be translated into clinical practice, several issues still need to be addressed in preclinical in vitro and in vivo models.