Human milk: insights on cell composition, organoids and emerging applications.

Abstract

Human milk is far more than a source of infant nutrition. It is a dynamic, living fluid packed with cells, bioactive molecules, and a complex microbiome that shapes neonatal development and lifelong health. Recent advances have illuminated the remarkable cellular diversity of human milk, including epithelial, immune, microbial and stem cells, each contributing essential biological functions. Milk contains distinct membrane-bound structures in the form of milk fat globules and extracellular vesicles that package a diverse cargo of lipids, proteins and nucleic acids for neonate nutrition, development and immune regulation. This review explores the composition of human milk, highlighting its nutrient and bioactive components and discussing growing concerns of xenobiotic and viral burden. We describe how milk-derived cells offer non-invasive windows into lactation biology and how emerging 3D mammary organoid models, particularly those generated from human milk cells, provide unprecedented tools to study breast development, lactation disorders, and regenerative therapies. We outline the potential of milk cells and extracellular vesicles in neonatal care, personalized medicine, and biobanking, while addressing current technical challenges and future research opportunities. By harnessing the unique properties of human milk, we stand at the threshold of transformative insights into maternal-infant health and novel biomedical applications. IMPACT: Up to date summary of bioactives, living cells and membrane bound compartments found in human milk. Primer on human mammary organoid technology, including advantages, recent advances and step by step methods. Highlights the unrealized potential of human milk in organoid technology, therapeutics, and regenerative medicine.