Abstract

Role of Extracellular Vesicles in Fetal Lung Morphogenesis Mediated by Mechanical Signals

Juan Sanchez-Esteban, Associate Professor of Pediatrics, Staff Neonatologist, Women & Infants Hospital of Rhode Island, Brown University

Incomplete development of the lung secondary to extreme prematurity or pulmonary hypoplasia can cause neonatal death and serious long-term morbidities. Currently, the management of these conditions is primarily supportive.  Lung morphogenesis has significant dependence on mechanical signals. However, the mechanisms by which mechanical forces accelerate lung development are not fully-characterized. Extracellular vesicles (EVs), including exosomes and microvesicles, are increasingly recognized as a novel mode of cell-to-cell communication. Shedding vesicles are released from many cell types and have been identified in a variety of body fluids. Moreover, EVs were found to be important for tissue morphogenesis in drosophila. However, the role of EVs in fetal lung development is unexplored. Our preliminary studies show the presence of EVs in the lumen of the fetal lung. In addition, physiologic levels of mechanical strain stimulate the release of EVs in fetal lung epithelial cells. Moreover, incubation of fetal epithelial cells with EVs mimics the effect of stretch on cell differentiation. These preliminary studies suggest that signaling mediated by EVs could be important for fetal lung development. Currently, we are investigating the role of EVs in fetal lung development using ex vivo and in vivo models.