Stem Cells in Breast Milk Might Help Baby Grow Up Strong

We have all probably heard about the benefits of breast milk for your baby as opposed to some other source of nutrition. This list of benefits is extensive: antibodies, better microfloral adaptation throughout the gastrointestinal tract, it helps you get your figure back, lower rates of illness in breast-fed babies, better for the environment, and so on. However, this long litany of benefits, and do not get me wrong, I am not knocking the benefits of breast-feeding, does not include one other benefit, and that includes a dose of breast-specific stem cells. Preliminary evidence has shown that mouse pups take in stem cells from their mother during breastfeeding, suggesting that the same thing might happen in humans.

Several years ago, it became clear that human breast milk contains a breast-specific kind of stem cells. This remarkable finding however did not answer the question of whether these cells coincidentally leaked into breast milk or they do anything useful with respect to the breast-feeding infant.

A presentation at the National Breastfeeding and Lactation Symposium in London last week presented data that suggests that, in mice at least, breast milk stem cells cross into the offspring’s blood from their stomach and play a functional role later in life.

Foteini Hassiotou from the University of Western Australia and her coworker used genetically modified mice whose cells contain a gene called tdTomato, which glows and intense shade of red under fluorescent light. The red-glowing females were mated and gave birth to mouse pups, but they were then presented with mouse pups from mothers who were genetically unmodified. Thus any red-glowing cells in these unmodified pups must have come to them from their mother’s milk.

When the these mouse pups that had been suckled by the tdTomato-expressing mothers grew to adulthood, assays of their tissues showed that red-glowing cells were found in their blood and the brain, thymus, pancreas, liver, spleen and kidneys. Hassiotou’s team also discovered that the breast-specific stem cells had differentiated into mature cells. Those red-glowing cells in the brain had the characteristic shape of neurons, those cells in the liver made the liver protein albumin, and those in the pancreas made insulin. According to Hassiotou, “They seem to integrate and become functional cells.”

What, precisely, is the role of these cells in the life of mice? Do they play a role in normal growth and development, or could they help to make the offspring tolerant to its mother’s cells and proteins, to reduce chances of an allergic reaction to her breast milk? “There must be some evolutionary advantage,” says Hassiotou.

According to Hassiotou, since her work and that of her colleagues clearly shows that these breast milk stem cells can differentiate into several different types of tissues makes it more likely they could be used for therapeutic applications. Chris Mason of University College London adds: “If these intriguing cells are functional, they could be a novel option for producing future cell therapies.”

Breast milk stem cells seem to have less capacity for unlimited cell division than embryonic stem cells. “But that’s actually a good thing,” says Hassiotou, because they do not form tumors when injected into mice. Therefore they may be less likely to trigger cancer if used to treat people.

Hassiotou points out that this kind of work cannot be done in humans, but she is planning to repeat it in a non-human primate species known as macaques.

Isolating Mammary Gland Stem Cells

Female mammary glands are home to a remarkable population of stem cells that grow in culture as small balls of cells called “mammospheres.” Clayton and others were able to identify these stem cells in 2004 (Clayton, Titley, and Vivanco, Exp Cell Res 297 (2004): 444-60), and Max Wicha’s laboratory at the University of Michigan showed that a signaling molecule called Sonic Hedgehog and a Polycomb nuclear factor called Bmi-1 are necessary for the self-renewal of normal and cancerous mammary gland stem cells (Lui, et al., Cancer Res June 15, 2006 66; 606). The biggest problem with mammary gland stem cells is isolating them from the rest of the mammary tissue.

Mammary gland stem cells or MaSCs are very important for mammary gland development and during the induction of breast cancer. Getting cultures of MsSCs is really tough because the MaSCs share cell surface markers with normal cells and they are also quite few in number.

Gregory Hannon and his co-workers at Cold Spring Harbor Laboratory used a mouse model to identify a novel cell surface protein specific to MaSCs. By exploiting this unusual marker, Hannon and his team were able to isolate MaSCs from mouse mammary glands of rather high purity.

Camila Do Santos, the paper’s first author, said that “We are describing a marker called Cd1d.” Cd1d is also found on the surfaces of cells of the immune system, but is specific to MaSCs in mammary tissue. Additionally, MaSCs divide slower than the surrounding cells. Do Santos and her colleagues used this feature to visually isolate MaSCs from cultured mammary cells.

They used a mouse strain that expresses a green glowing protein in its cells and then made primary mammary cultures from these green glowing mice. After shutting of the expression of the green glowing protein with doxycycline, the cultured cells divided, and diluted the quantity of green glow protein in the cells. This caused them to glow less intensely. However, the slow-growing MaSCs divided much more slowly and glowed much more intensely. Selecting out the most intensely glowing cells allowed Dos Santos and her colleagues to enrich the culture for MaSCs.

“The beauty of this is that by stopping GFP expression, you can directly measure the number of cell divisions that have happened since the GFP was turned off,” said Dos Santos. She continued: “The cells that divide the least will carry GFP the longest and are the ones we characterized.”

Using this strategy, Dos Santos and others selected stem cells from the mammary glands in order to examine their gene expression signature. They also confirmed that by exploiting Cd1d expression in the MaSCS, in combination with other techniques, they could enhance the purity of the cultures several fold.

Hannon added, “With this advancement, we are now able to profile normal and cancer stem cells at a very high degree of purity, and perhaps point out which genes should be investigated as the next breast cancer drug targets.”

Will we be able to use these cell for therapeutic purposes some day?  Possibly, but at this time, more must be known about them and MaSCs must be better characterized.