Epithelial and mesenchymal stem cell biology in the mammary gland: mechanisms, comparative insights, and translational perspectives
Year: 2026
Type: review
Abstract: Mammary stem cell biology provides an important link between tissue regeneration, mammary development, metabolic adaptation, inflammation, and lactational function. This review examines epithelial and mesenchymal stem cell populations in the mammary gland, with emphasis on their complementary roles and interactions within the tissue microenvironment. Evidence from murine, human, and bovine studies is integrated to highlight common biological principles as well as species-specific features relevant to mammary function and disease. Particular attention is given to the dynamic interactions among epithelial, stromal, immune, endocrine, and metabolic components of the mammary niche and to how these interactions regulate stem cell activity and tissue homeostasis. Metabolic regulation is illustrated by the role of mechanistic target of rapamycin complex 1 (mTORC1) in mammary epithelial stem cell regulation. Evidence from the mammary gland indicates that intermittent mTORC1 inhibition can increase stem-cell activity, with potential effects on mammary development, lactational capacity, and persistency, although effects on whole-animal milk production remain to be established. Mesenchymal stem cells are considered both as resident mammary stromal populations and as potential external mediators of epithelial-stromal communication. They may integrate metabolic, endocrine, and inflammatory signals and contribute to tissue homeostasis and repair. Their therapeutic potential is further discussed in the context of bovine mastitis, where mesenchymal stem cell-based approaches remain experimental and may act through paracrine, immunomodulatory, and experimentally supported antimicrobial mechanisms. Collectively, current evidence supports distinct but complementary roles of epithelial and mesenchymal stem-cell populations in mammary development, regeneration, and tissue maintenance, although their identity and functional significance remain incompletely resolved across species. Defining these populations and their interactions may inform stem cell-based approaches to mammary health and regeneration in humans and to health and production in farm animals.
Author: Itamar Barash
Institution: Agricultural Research Organization
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7223356725