Extracellular vesicles from mesenchymal stromal cells: an emerging therapy for intractable neonatal disorders

Abstract Neonatal disorders affecting different organs are highly multifactorial and involve a complex interplay among prematurity, inflammation, oxidative stress, tissue injury, immune dysregulation, and impaired regeneration. Conditions such as hypoxic-ischemic encephalopathy, intraventricular hemorrhage, neonatal stroke, bronchopulmonary dysplasia, and necrotizing enterocolitis often result from or cause multi-organ dysfunction. This multifaceted nature presents a substantial therapeutic challenge, as current treatment plans are largely supportive and are limited to addressing the underlying immaturity and injury. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have emerged as promising cell-free therapeutics owing to their ability to modulate inflammation, promote repair, and support organ maturation. By delivering a rich secretome of proteins, lipids, and regulatory RNAs, MSC-EVs retain the regenerative benefits of mesenchymal stromal cells while offering improved safety and storage. This review provides a comprehensive overview of MSC-EV therapy for neonatal disorders, focusing on the mechanisms of action, preclinical evidence, and future perspectives on clinical translation. By integrating the currently available study findings, this review highlights the potential of MSC-EVs as a multifaceted therapy for preterm infants, capable of addressing both tissue injury and developmental immaturity.