# Therapeutic potential and translational challenges of extracellular vesicles in neonatal medicine

## TL;DR

Extracellular vesicles show promise for treating neonatal diseases but face challenges in standardization and safety before clinical use.

## Contribution

The paper reviews the therapeutic potential and translational challenges of extracellular vesicles in neonatal medicine.

## Key findings

- EVs reduce inflammation and preserve tissue integrity in neonatal disease models.
- Clinical translation is hindered by inconsistent isolation methods and safety data gaps.
- Early trials for BPD and HIE suggest potential for EV-based neonatal therapies.

## Abstract

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.

Potential therapeutic effects of extracellular vesicles (EVs) on major neonatal diseases. EVs exert anti‐inflammatory, anti‐apoptotic, and regenerative actions in neonatal sepsis, necrotizing enterocolitis, hypoxic–ischemic encephalopathy, and respiratory distress syndrome. Mechanistic pathways involve modulation of cytokines, immune cell activation, neuroprotection, angiogenesis, and barrier integrity.