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Breast: Stem and Progenitor Cells in Adults

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The mammalian breast is one of the few organs in the female body that undergoes large changes during the life cycle. Puberty, pregnancy, and lactation are some of the physiological processes that dramatically alter the nature and cellular composition of the breast. This article discusses the stem and progenitor cell populations present in the breast that allow for this inherent regenerative capacity in the breast.

The breast has a branched network of ducts and lobules that comprises the glandular tissue responsible for producing milk during lactation. It is also comprised of a layer of myoepithelial cells that have muscle-like contractile ability that can contract to allow for milk extraction from the mammary glands into the ducts that carry the milk. In essence, there are three major cell types in the glands and ducts of the breast. The luminal, or outward-facing alveolar cells, and the layer of myoepithelial cells that form a basal layer below the alveolar cells make up the glandular portion. The ductal cells line the epithelial layer of the ducts. These cells arise from two lineages, the luminal and myoepithelial. The alveolar and ductal cells described above arise from the luminal lineage. These three cell types are thought to originate from a common progenitor stem cell. Several other cell types exist in the breast, including a large amount of adipose cells that make up the fat pads in the breast and stromal cells in the connective tissue of the breast. Stem and progenitor cells in the breast, which are the focus of this article, are predominantly present to the glands where myoepithelial and alveolar cells are present. In particular, the major population of multipotent stem cells discovered in the breast is restricted to the basal layer of the glands.

During puberty, cell growth causes the branching and elongation of the epithelial ducts. After puberty, cycles of both proliferation and differentiation occur, with the estrous cycle accounting for the growth and decay of the alveolar tissue.

During pregnancy, the breast undergoes extensive changes, with a dramatic increase in the glands and ducts to allow for milk production in the lactating period. After lactation, the glands undergo involution as a result of cell death and return to their prepregnant state. The ability of the breast cell types to proliferate, involute, and proliferate again with each pregnancy presented the first clues for the presence of a stem cell type in the breast that can serve as the origin of the epithelial cell types.

Evidence that pointed toward the presence of mammary stem or progenitor cells with regenerative capacity in the breast came from transplantation experiments done in mice as early as the 1960s. Research studies found that serial transplantations (described below) of epithelial cells into empty fat pads of other mice resulted in the regeneration of all the epithelial cell lineages for several successive generations. The presence of stem cells in these studies was indicated by the fact that the transplanted cells satisfied the two important criteria for being stem cells: the ability to differentiate into multiple lineages and the ability to self-renew. The sections below detail the methods of identifying mammary stem cells, the discovery of stem and progenitor cells, and the types of stem cells that have been proposed to give rise to the epithelial cell lineages in the breast.

The SAGE Encyclopedia of Stem Cell Research

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