Extracellular matrix context shapes morphogenesis and lactation-associated states in human milk-derived mammary organoids
The mammary gland relies on reciprocal interactions between epithelial cells and their surrounding extracellular matrix (ECM) to form and maintain milk-producing tissue structures. Yet these processes remain difficult to study in human model systems. Mammary epithelial cells (MECs) can be isolated noninvasively from breast milk, but whether they generate three-dimensional organoids and respond to…
Mammary glands depend on the interplay between epithelial cells and their surrounding extracellular matrix (ECM) to create and sustain milk-producing tissue. However, studying these processes in human models proves challenging. Mammary epithelial cells (MECs), which can be noninvasively extracted from breast milk, have shown the ability to generate three-dimensional organoids, but it remains uncertain if they respond to matrix cues.
In this study, researchers cultured milk MECs in decellularized mammary ECM (dECM), Matrigel, and collagen I to determine the impact of matrix composition on organoid formation and function. In dECM, the milk MECs developed polarized branched networks with aligned actin organization along collagen fibrils. Conversely, when cultivated in Matrigel, the cells exhibited a state more closely associated with lactation, characterized by the expression of beta-casein and the production of milk fat globules.
These findings demonstrate that breast milk-derived MEC organoids present a valuable human model for investigating how ECM context influences mammary morphogenesis and lactation biology.
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