J Clin Neonatol. 2013 Jan-Mar; 2(1): 17.

Neonatal Intensive Care Unit and Laboratory of Neonatal Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

1Neonatal Intensive Care Unit, Azienda Ospedaliera Santi Antonio e Biagio e Cesare Arrigo, Alessandria, Italy

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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.

Keywords: Bronchopulmonary dysplasia, bronchopulmonary, endothelial, EPC, mesenchymal, MSC, newborn, periventricular leukomalacia, preterm, progenitor cells, periventricular leukomalacia, stem cells

Very and extremely preterm infants suffer from severe diseases associated with premature birth, including bronchopulmonary dysplasia (BPD), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), sepsis and retinopathy of prematurity (ROP). During the 90s, the universal introduction of antenatal steroids and surfactant replacement as standard therapies for the prevention and treatment of neonatal respiratory distress syndrome (RDS) in the neonatal intensive care units (NICUs) has dramatically changed the natural history of diseases affecting prematurely born infants.

Indeed, together with a reduction in the severity of neonatal RDS, the sequelae of perinatal lung and brain injury profoundly changed: The old BPD and cystic PVL were replaced by newly emerging diseases, the so-called new BPD and noncystic, diffuse PVL, respectively. These new sequelae differ from the old ones in severity (in general are less severe), pathogenesis, pathological features and clinical presentation.[1,2,3,4,5,6] In general, focal injury/necrosis and the consequent fibrosis/astrogliosis, the main components of old BPD and cystic PVL, appear to be milder and to contribute to a lesser extent to the pathogenesis of new BPD and noncystic PVL. Conversely, tissue simplification and developmental arrest (larger and fewer alveoli in the lungs and hypomyelination with defective white matter development and neuronal abnormalities in the brain) are the key and predominant components of new BPD and of the diffuse, noncystic form of PVL.[3,6]

While surfactant replacement and prenatal steroid proved revolutionary in changing the destiny of premature infants during the 90s, no preventive strategy is currently available to reduce the incidence of these emerging diseases, and the prevalence of all complications of prematurity has reached a steady state across the last decade []. Overall, the sequelae of prematurity still represent a burden for neonatal medicine and global health.

Incidence of major diseases associated with preterm birth in a population of very low birth weight infants (<1500 g)

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Stem Cell Therapy for Neonatal Diseases Associated with ...