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Derived from diverse sources such as mesenchymal stem cells, breast milk, and even non\u2010animal systems, EVs exhibit potent anti\u2010inflammatory, immunomodulatory, and tissue\u2010regenerative 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\u2010compliant safety assessments is essential to establish clinical readiness. Current early\u2010phase clinical trials targeting neonatal BPD, prevention of prematurity\u2010related brain injury, and HIE indicate growing translational momentum. If these challenges are addressed, EV\u2010based therapeutics could transform neonatal care, reducing mortality and long\u2010term disability in vulnerable preterm and term infants.<\/jats:p>","DOI":"10.1002\/btm2.70093","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T12:01:19Z","timestamp":1764072079000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic potential and translational challenges of extracellular vesicles in neonatal medicine"],"prefix":"10.1002","volume":"11","author":[{"given":"Ali M.","family":"Atoom","sequence":"first","affiliation":[{"name":"Faculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research Al\u2010Ahliyya Amman University  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Media","family":"Hamed\u2010Ahmed","sequence":"additional","affiliation":[{"name":"Department of Anesthesia 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