So what exactly are stem cells. Stems cells are cells that have the potential to become any type of cell in the body. One of the main characteristics of stem cells are their ability to self-renew or multiply while maintaining the potential to develop into other types of cells (2). In the 3- to 5-day- old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lung, skin, sperm, eggs and other tissues. Scientists have worked with two different stem cells from animals and humans: embryonic stem cells and adult stem cells (2). Embryonic stem cells are stem cells found in the embryo that are capable of dividing without differentiating and are known to develop into cells and tissues of the three primary germ layers- endoderm (interior stomach lining, gastrointestinal tract, the lungs), mesoderm (muscle, bone, blood, urogenital system), or ectoderm (epidermal tissues and nervous system) (1). On the other hand, adult stem cells are rare, undifferentiated cells found in many organs and differentiated tissues with a limited capacity to differentiate to cell types only in the organ of origin (2).
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Stem cells can yield vital information about the complex events that occur during human development. Understanding how undifferentiated stem cells become differentiated cells that form tissues and organs is furthering science and clinical research. For example, stem cells can be used to test new medications for safety on differentiated cells or cell-based therapies can be perfected to treat such pervasive and debilitating diseases as Alzheimer's, heart disease, or diabetes. One of the obstacles that has hindered further research has been the invasiveness of obtaining undifferentiated, pluripotent stem cells. However, the recent findings into the pluropotency in human breastmilk stem cells (hBSCs) may provide just the perfect alternative (2).
Presence of stem cells in Human Breast Milk
The presence of adult stem cells in mammary tissue had been known to occur in mammary glands and was first postulated based on the capacity for mammary epithelium to significantly expand and regress in a repeated fashion throughout adult life (1). Similarly, mammary stem cells were implicated in the onset and progression of invasive breast cancers, which suggest that these stem cells have unique self-renewal capabilities (3). However, it wasn't until 2007 when Cregan et al. established the presence of stem cells in human breast milk (4). Stem cells in mammary tissue had been reported to contain stem cell markers cytokeratin (CK) 5, CK14, CK18 and CK19FH. Stem cells makers are essentially genes and their protein products used by scientists to identify certain types of cells (2). To identify whether these markers were also present in cells from human breastmilkFH, cultured cells from human breastmilk were studied using the multipotent stem cell marker nestin. Cells in the culture were identified positive for nestin thus suggesting that human breastmilk is a potential source for mammary stem cells (4). Stem cells and differentiated cells from the lactating epithelium enter the breastmilk either through cell migration and/or as a consequence of the mechanical shear forces of breastfeeding (5).FH
Multipotency of hBSCs established
Nevertheless, although Cregan et al. were able to demonstrate the presence of nestin positive stem cells in human breast milk, their research efforts failed to explain the differentiation potential of these mammary cells isolated from human breastmilk (6).Â FHThus, in 2010, a team of researchers in India convened to look into the multipotent nature of hBSCs. To do so they isolated and expanded a mesenchymal (arising from the mesoderm germ layer during development) stem cell-like population from human breast milk. It had already been established that mesenchymal stem cells (MSCs), cells that can differentiate into a variety of cell types, could be isolated from different sources, namely bone marrow, adipose tissues, tendon, amniotic fluid, and menstrual blood; however, the mesenchymal stem cell nature of human breastmilk stem cells was yet to be established (7). The cultured cells were examined and were found positive for mesenchymal stem cell markers CD44, CD29, and SCA-1 confirming their identity as mesenchymal stem cells (6). Thus, the concerted research efforts of Patki et al. further corroborated Cregan et al.'s findings of the multipotent nature of hBSCs.
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An exciting research breakthrough occurred in 2012, when Dr. Hassiotou and her colleagues from the University of Western Australia established that pluripotent stem cells-cells that can divide into any of the three types of germ layers and thus give rise to nay fetal or adult cell type-are active in the lactating breast (1). Breastmilk samples were collected from different donors and the cultured cells displayed variable expression of pluripotency genes normally only found in human embryonic stem cells (hESCs) and were able to differentiate in vitro into cell lineages of all three germ layers (1). Furthermore, the pluripotency genes found in hBSCs included transcription factors (TFs), proteins that bind to specific DNA sequences and control the transcription of genetic information from DNA to mRNA, that are known to constitute the core "self-renewal circuitry" of hESCs. This type of cell population was only evident in the lactating breast and completely absent in the normal, resting, non-lactating breast, which indicates that there perhaps are some lactation-associated hormonal cues that activate this cell population (1).
Implications for infant nutrition
The discovery of pluripotent hBSCs provides a complete, noninvasive alternative for regenerative biology and developmental biology. In essence, stem cells from breastmilk can now be directed to become other body cell types such as bone, fat, liver and brain cells. One developmental biology question that this new discovery probes at is what connection exists between hBSCs and development of babies. Stem cell exchange between the mother and the embryo occurs in utero, and as Dr. Hassiotou has suggested through her work, this may continue postnatally via breastfeeding (1). It has been previously demonstrated that breastmilk leuokocytes, white blood cells that help fight off infection, enter the infant's systematic circulation (8, 9). Dr. Hassiotou proposes that hBSCs may also enter the systemic circulation and contribute to tissue repair and regeneration in the infant. Such a claim, if true, would have tremendous implications for public policy related to early infant nutrition. As it is, it has already been demonstrated that feeding of human breastmilk during the newborn intensive care unit (NICU) stay reduces the risk of short-and-long-term morbidities in premature infants (10). Breastfeeding behavior in the United States is heavily influenced by social norms: bottle feeding is viewed by many as the "normal" way to feed infants and the widespread exposure to substitutes for human milk, typically fed to infants via bottles, is largely responsible for the development of this norm (11). hBSCs emerge as a non-invasive, ethical and plentiful source of pluripotent stem cells that may be used in regenerative medicine and will have a direct effect in medical science as well as infant and maternal health in the forthcoming years. Nature function marvelously that it almost comes as no surprise that something so natural as human breastmilk could confer such wonderful benefits.