Therapeutic potential and translational challenges of extracellular vesicles in neonatal medicine

Extracellular vesicles (EVs) have emerged as promising therapeutic candidates for a range of neonatal diseases, including sepsis, necrotizing enterocolitis, hypoxic-ischemic encephalopathy (HIE), and bronchopulmonary dysplasia (BPD). Derived from diverse sources such as mesenchymal stem cells, breast milk, and even non-animal systems, EVs exhibit potent anti-inflammatory, immunomodulatory, and tissue-regenerative properties. Preclinical studies in neonatal models demonstrate their ability to reduce inflammation, preserve epithelial and endothelial barrier integrity, modulate immune cell phenotypes, and mitigate organ damage. Despite these encouraging findings, several critical barriers hinder their clinical translation. Challenges include incomplete characterization of EV molecular cargo, variability in isolation and quantification methods, lack of standardized dosing protocols, and limited safety data, particularly regarding procoagulant activity and thrombotic risk. The development of standardized, reproducible isolation techniques, rigorous molecular profiling, and GLP-compliant safety assessments is essential to establish clinical readiness. Current early-phase clinical trials targeting neonatal BPD, prevention of prematurity-related brain injury, and HIE indicate growing translational momentum. If these challenges are addressed, EV-based therapeutics could transform neonatal care, reducing mortality and long-term disability in vulnerable preterm and term infants.