Therapeutic Applications of Extracellular Vesicles: Perspectives from Newborn Medicine.

With the advancements in antenatal steroid therapies and surfactant replacement, current clinical practices in neonatal intensive care units allow the survival of infants at very low gestational age. Despite these advances, there continues to be significant morbidity associated with extreme preterm birth that includes both short-term and long-term cardiorespiratory impairment. With no effective single therapy in preventing or treating developmental lung injuries, the need for new tools to treat and reduce risk of complications associated with extreme preterm birth is urgent. Stem cell-based therapies, in particular therapies utilizing mesenchymal stem (stromal) cells (MSCs), have shown promise in a number of animal models of lung pathologies relevant to neonatology. Recent studies in this field have consolidated the concept that the therapeutic mechanism of MSC action is paracrine, and this led to wide acceptance of the concept that the delivery of the MSC secretome rather than live cells may provide an alternative therapeutic approach for many complex diseases. Here, we summarize the significance and application of cell-free based therapies in preclinical models of neonatal lung injury. We emphasize the development of extracellular vesicle (EV)-based therapeutics and focus on the challenges that remain to be addressed before their application to clinical practice.