Work

Extracellular Vesicles and Choline Metabolism in Neonatal Bronchopulmonary Dysplasia: A Systems-Pharmacology Framework for Regenerative Therapy

Year: 2026

Type: review

Abstract: Bronchopulmonary dysplasia (BPD) affects not only the lungs but also the lung-brain axis, leading to neuroinflammation and white matter dysmaturation. Current therapies for BPD treat the lung manifestations but do not address the multi-organistic signaling network essential for neonatal development. Here, we describe a regenerative medicine-based approach to treat BPD by employing the extracellular vesicle (EV) and choline pathways to restore developmental homeostasis. Mesenchymal cell-derived EVs transport bioactive lipids, proteins, and microRNAs to target cells to resolve inflammation and stabilize the endothelial barrier. At the same time, choline and its derivatives regulate phosphatidylcholine and S-adenosylmethionine synthesis to preserve cellular membrane integrity and epigenetic marks. The systems-pharmacology hypothesis that EV-mediated signaling and choline-dependent phospholipid and one-carbon metabolism may have complementary effects on inflammatory, vascular, and neurodevelopmental pathways is supported by available mechanistic evidence. Thus, the combined effect of the EV and choline pathways represents a highly translational and network-based therapy to treat BPD and protect the lung-brain axis.

Source: International Journal of Nanomedicine

DOI: 10.2147/ijn.s639450