Human milk contains PLURIPOTENT stem cells

• Stem cells are present in human breast milk.
• These cells can become many different kinds of cells.
• The cells can be non-invasively collected and studied in vitro.
• These findings have implications for infant development and regenerative medicine.

Last month during the Bi-Annual Meeting of the International Society for Research in Human Milk and Lactation in gorgeous Trieste, Italy, one could hear a pin drop when Dr. Foteini Hassiotou presented her and colleagues’ ground-breaking work on human stem cells in breast milk.

Most of us are familiar with embryonic stem cell research as potentially revolutionary for medical science and human health. This is because during embryonic

development, all of our adult tissues derive from three initial germ layers – the endoderm, the mesoderm, and the ectoderm. In this way, embryonic stem cells are pluripotent, which means that the cells have the capability to develop into any of the 200 cell types in our body. However, significant controversy surrounds embryonic stem cell research, constraining research efforts on this topic. Adult stem cells exist, but they are generally more limited in terms of the types of cells they can become- known as multipotent. Although the presence of adult stem cells had been known to occur in mammary tissue, the presence of stems cells in breast milk was established by Cregan and collegues in 2007. Their initial research suggested that these cells were multipotent and could develop into a limited number of subsequent cell types. In 2010, the multipotent features of stem cells in breast milk was confirmed by researchers in India (Patki et al., in 2010).

Dr. Hassiotou and colleagues have now established that pluripotent stem cells are active in the lactating breast and can be non-invasively collected from breast milk (2012). Embryonic stem cells have a “core-circuitry of self-renewal” through the transcription of particular genes (OCT4, SOX2, NANOG, SSEA4, & three transcription factors (TFs)) (Hassiotou et al., 2012). hBSC show similar patterns of gene activity that allow for the stem cells to replicate. hBSC were not found in nonactive mammary tissue. Rather, hormonal cues during pregnancy and lactation seemingly activate the stem cells within the mammary gland. Moreover, hBSC are localized within particular areas of the lactating breast. For example, cells expressing TFs were more prevalent in the myoepithelial layer, but much less prevalent in the lumen, ducts, or alveoli. Most excitingly, in vitro investigation of hBSC revealed that cells differentiated into cell types of all three germ layers, suggesting pluripotency. For example, hBSC can become neural cells and cells that express insulin, including many others!

In general, discussion of stem cells usually turns to regenerative medicine. Proponents for developing stem cell therapies hypothesize that stem cells could be used to treat patients with spinal injuries, neurodegenerative disorders such as Parkinson’s, or Type I diabetics, whose islet cells in the pancreas no longer produce insulin. However, from an developmental biological perspective, I am most intrigued about what these hBSC may do when ingested by the infant. Hassiotou and colleagues suggest that hBSC may behave similarly to immunofactors in the infant, crossing into the infant’s bloodstream and playing a role in tissue repair and development.

The discovery of pluripotent stem cells in human milk is a game changer, whether your perspective is regenerative medicine or developmental biology. Research on pluripotent stem cells can now potentially rely on hBSC collected non-invasively, reducing reliance on human embryonic stem cell research. Within the neonate, these stem cells ingested via breast milk may contribute to developmental programming for health and metabolism later in life. We can further hypothesize that stem cells in breast milk may be critically important for tissue development and repair in pre-term and NICU infants. Although there are only a handful of studies on this topic, the implications of this discovery cannot be overstated. I know I am not alone among my colleagues in eagerly anticipating the next discoveries in human breast milk stem cells.