Umbilical Cord Blood Cells Do Not Reduce Ventilation-Induced Lung Injury in Preterm Lambs

Mesenchymal stem cells (MSCs) are currently being widely investigated both in the lab and in clinical trials for multiple disease states. The differentiation, trophic, and immunomodulatory characteristics of MSCs contribute to their therapeutic effects. Another often overlooked factor related to efficacy is the degree of engraftment. When reported, engraftment is generally low and transient in nature. MSC delivery methods should be tailored to the lesion being treated, which may be local or systemic, and customized to the mechanism of action of the MSCs, which can also be local or systemic. Engraftment efficiency is enhanced by using intra-arterial delivery instead of intravenous delivery, thus avoiding the “first-pass” accumulation of MSCs in the lung. Several methodologies to target MSCs to specific organs are being developed. These cell targeting methodologies focus on the modification of cell surface molecules through chemical, genetic, and coating techniques to promote selective adherence to particular organs or tissues. Future improvements in targeting and delivery methodologies to improve engraftment are expected to improve therapeutic results, extend the duration of efficacy, and reduce the effective (MSC) therapeutic dose.

Bronchopulmonary dysplasia (BPD) remains the most common severe complication of preterm birth. A number of recent animal models and clinical studies provide new information about pathophysiology and treatment. The epidemiology of BPD continues to demonstrate that birth weight and gestational age are most predictive of BPD. Correlations of BPD with chorioamnionitis are clouded by the complexity of the fetal exposures to inflammation. Excessive oxygen use in preterm infants can increase the risk of BPD but low saturation targets may increase death. Numerous recent trials demonstrate that many preterm infants can be initially stabilized after delivery with continuous positive airway response (CPAP) and then be selectively treated with surfactant for respiratory distress syndrome. The growth of the lungs of the infant with BPD through childhood remains poorly characterized. Recent experiences in neonatology suggest that combining less invasive care strategies that avoid excessive oxygen and ventilation, decrease postnatal infections, and optimize nutrition may decrease the incidence and severity of BPD.

Bronchopulmonary dysplasia is a chronic lung disease that affects premature babies and contributes to their morbidity and mortality. Improved survival of very immature infants has led to increased numbers of infants with this disorder. This increase puts a heavy burden on health resources since these infants need frequent re-admission to hospital in the first 2 years after birth and, even as adolescents, have lung-function abnormalities and persistent respiratory symptoms. Unlike the original description of the disease in 1967, premature infants can develop chronic oxygen dependency without severe, acute respiratory distress; this "new bronchopulmonary dysplasia" could be the result of impaired postnatal lung growth. Whether such infants subsequently have catch-up lung growth, especially if given corticosteroids postnatally, is unknown. No safe and effective preventive therapy has been identified, but promising new treatments directed either at reducing lung injury or improving lung growth are under study.