Mammary organoids: Advances, applications, and future perspectives in animal science and biotechnology

Abstract

Organoids have emerged as powerful in vitro models that bridge the gap between traditional two-dimensional cultures and in vivo studies. Over the past decade, advances in stem cell biology and extracellular matrix (ECM) engineering have enabled the establishment of organoids that partially recapitulate the structural and functional features of the mammary gland. These models have provided new opportunities to investigate mammary development, lactation biology, and breast cancer. In this review, we summarize recent progress in the establishment of mammary organoids across species, including humans, mice, and livestock. We discuss the effects of cell source, ECM, and growth factors on organoid culture. We further highlight the applications of organoid culture in mammary gland development, lactation biology, drug screening, precision medicine, and cell-based milk production. Despite the large advances achieved in the technique, the current mammary organoid culture still has many limitations due to the incomplete understanding of tissue complexity, insufficient vascularization, loss of microenvironmental interactions, and challenges in reproducibility. Emerging strategies, such as multi-organ systems, three-dimensional bioprinting, and organoids-on-a-chip, offer promising approaches to improve the physiological relevance of this technique and functional maturity. Overall, mammary organoids represent a rapidly evolving platform with broad applications. They are expected to become important platforms linking mammary biology to livestock production and next-generation dairy biomanufacturing.