• Open Access

Breastmilk Is a Novel Source of Stem Cells with Multilineage Differentiation Potential§

Authors

  • Foteini Hassiotou,

    Corresponding author
    1. School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia
    2. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia
    • School of Chemistry and Biochemistry, The University of Western Australia, 35 Stirling Highway, Crawley, Western Australia 6009, Australia

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    • Telephone: +61-433-528-943; Fax: +61-8-6488-7086

  • Adriana Beltran,

    1. Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Ellen Chetwynd,

    1. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Alison M. Stuebe,

    1. Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Alecia-Jane Twigger,

    1. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia
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  • Philipp Metzger,

    1. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia
    2. Institute of Biochemistry and Molecular Biology, ZBMZ, University Freiburg, Germany
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  • Naomi Trengove,

    1. School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia
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  • Ching Tat Lai,

    1. School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia
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  • Luis Filgueira,

    1. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia
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  • Pilar Blancafort,

    1. School of Anatomy, Physiology and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia
    2. Department of Pharmacology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
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  • Peter E. Hartmann

    1. School of Chemistry and Biochemistry, The University of Western Australia, Crawley, Western Australia, Australia
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  • Authors contributions: F.H.: conception and design, financial support, collection and assembly of data, data analysis and interpretation, manuscript writing, and final approval of manuscript; A.B.: animal injections and monitoring and final approval of manuscript; E.C.: provision of study participants and final approval of manuscript; A.M.S.: provision of study participants, financial support, and final approval of manuscript; A.-J.T. and P.M.: collection of data and final approval of manuscript; N.T. and C.T.L.: intellectual input and final approval of manuscript; L.F., P.B., and P.E.H.: conception and design, financial support, data analysis and interpretation, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS August 3, 2012.

Abstract

The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation. The scarcity of human lactating breast tissue specimens and the low numbers and quiescent state of MaSCs in the resting breast have hindered understanding of both normal MaSC dynamics and the molecular determinants that drive their aberrant self-renewal in breast cancer. Here, we demonstrate that human breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk cells from different donors displayed variable expression of pluripotency genes normally found in human embryonic stem cells (hESCs). These genes included the transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self-renewal circuitry of hESCs. When cultured in the presence of mouse embryonic feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC-like colony morphology and phenotype and could be passaged in secondary and tertiary clonogenic cultures. While self-renewal TFs were found silenced in the normal resting epithelium, they were dramatically upregulated in breastmilk cells cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro into cell lineages from all three germ layers. These findings provide evidence that breastmilk represents a novel and noninvasive source of patient-specific stem cells with multilineage potential and establish a method for expansion of these cells in culture. They also highlight the potential of these cells to be used as novel models to understand adult stem cell plasticity and breast cancer, with potential use in bioengineering and tissue regeneration. STEM Cells2012;30:2164–2174

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