At the dawn of a new discovery: the potential of breast milk stem cells - PubMed (original) (raw)

Review

At the dawn of a new discovery: the potential of breast milk stem cells

Foteini Hassiotou et al. Adv Nutr. 2014.

Abstract

Breast milk contains bioactive molecules that provide a multitude of immunologic, developmental and nutritional benefits to the infant. Less attention has been placed on the cellular nature of breast milk, which contains thousands to millions of maternal cells in every milliliter that the infant ingests. What are the properties and roles of these cells? Most studies have examined breast milk cells from an immunologic perspective, focusing specifically on the leukocytes, mainly in the early postpartum period. In the past decade, research has taken a multidimensional approach to investigating the cells of human milk. Technologic advances in single cell analysis and imaging have aided this work, which has resulted in the breakthrough discovery of stem cells in breast milk with multilineage potential that are transferred to the offspring during breastfeeding. This has generated numerous implications for both infant and maternal health and regenerative medicine. This review summarizes the latest knowledge on breast milk stem cells, and discusses their known in vitro and in vivo attributes as well as potential functions and applications.

© 2014 American Society for Nutrition.

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Conflict of interest statement

Author disclosures: F. Hassiotou and P. E. Hartmann, no conflicts of interest.

Figures

FIGURE 1

FIGURE 1

Cross-sectional view of the human lactating breast, showing mature alveoli (A). The epithelial cell adhesion molecule is shown in green. Each alveolus comprises a luminal layer of epithelial cells that contains the lactocytes, expressing milk proteins such as α-lactalbumin (shown in red) (B). Myoepithelial cells lining alveoli in the lactating breast (C). Smooth muscle actin is shown in green; nuclei are shown in blue (DAPI stain). Scale bars: 10 μm.

FIGURE 2

FIGURE 2

Anatomy of the human adult breast in its resting state (in nonpregnant, nonlactating women) (A) and its lactating state (B). During pregnancy and lactation, elongation of existing ducts and synthesis of new ducts occur, along with formation of alveolar structures at the duct termini, where milk is synthesized during lactation. Reproduced with permission from Medela AG.

FIGURE 3

FIGURE 3

CK5+ cells (shown in green) in culture derived from breast milk (A). Scale bar: 50 μm. CK5+ cells (shown in green) in the alveoli (B1) and ducts (B2) of the lactating mammary epithelium. Scale bars: 10 μm. In B2, CK5+ cells are also evident in the ductal lumen, supporting their presence in breast milk. Nuclei are shown in blue (DAPI stain). CK5+, cytokeratin 5+.

FIGURE 4

FIGURE 4

Human resting breast tissue showing minimal expression of stem cell markers CD49f (shown in red) and CD29 (shown in green) (A). Human lactating breast depicting upregulation of these stem cell markers, which are mostly restricted to the basal layer in the featured duct (B). Scale bars: 10 μm. Nuclei are shown in blue (DAPI stain).

FIGURE 5

FIGURE 5

Expression of pluripotency genes by freshly isolated breast milk cells at the protein level [immunofluorescence images; nuclei are shown in blue (DAPI stain)] and at the mRNA level (bar blot for 17 breastfeeding women—S1–S17—comparing expression with fibroblasts, resting breast cells, and hESCs) (A). In vitro differentiation of hBSCs into cells from all 3 germ layers (B). Under mammary differentiation conditions, hBSCs form mini-mammary glands (with primary, secondary, and tertiary structures) in the culture dish secreting milk proteins (C). A and B are adapted with permission from (18). hBSC, human breast milk stem cell; hESC, human embryonic stem cell; KLF4, Kruppel-like factor 4; NANOG, nanog homeobox; OCT4, POU class 5 homeobox 1; OSX, Sp7 transcription factor; PDX1, pancreatic and duodenal homeobox 1; RUNX2, runt related transcription factor 2; SOX2, sex determining region Y-box 2; SOX6, sex determining region Y-box 6; SSEA4, stage-specific embryonic antigen 4.

FIGURE 6

FIGURE 6

The current knowledge of the cellular hierarchy and different cell types of human milk.

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