The cellular hierarchy of human breastmilk: novel insights into breastmilk stem cells

[Truncated abstract] Further to its nutritional components, breastmilk also contains maternal cells, the properties and role(s) of which are poorly understood. The primary aim of this thesis was to examine the properties and hierarchy of breastmilk cell populations. First, temporal patterns in breastmilk cell content were examined. Second, the variability in breastmilk leukocyte content and response to infection were established. Third, the presence of stem cells in breastmilk was studied, focusing on their origin, properties and potential functions. Finally, stem cell populations were compared between the normal resting and lactating breast, and breast tumours with lactating features in an effort to elucidate molecular determinants of lactation and normal or aberrant self-renewal. Examination of temporal variations in breastmilk cell content demonstrated a close association with breast fullness. Previous work has demonstrated that pre-feed milk contains lower cell and fat contents than post-feed milk. Here, w e identified a further increase in both breastmilk cell and fat contents at approximately 30 min post-feeding, with a subsequent decrease as the breast synthesised milk. This new knowledge is critical in standardising breastmilk sampling protocols in lactation studies, and may also be used as a basis for further study of the mechanisms behind cell movement into breastmilk. Previous literature has reported a great variability in breastmilk leukocyte content. To elucidate this, we investigated the leukocyte content of milk from different lactation stages. Colostrum had high leukocyte levels (13-70% of total cells) that decreased to a low baseline range (0-2%) in mature breastmilk. This low level was maintained throughout lactation unless the mother and/or her infant became infected, when it increased and was then restored upon recovery.