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Characterization of Human Mammary Epithelial Stem Cells

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Annual summary rept. 15 Sep 2006-14 Sep 2007

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The mammary epithelium in normal adult female mice contains undifferentiated stem cells with extensive in vivo regenerative and self-renewal potential. Analogous cells presumably exist in the mammary glands of adult women, and may be the target cells for transforming mutations that lead to the evolution of breast cancer stem cells. The objective of this grant is to develop a robust, reproducible and specific assay for normal human mammary stem cells, based on a recently-developed xenotransplant methodology. The assay will be applied to identify stem cell markers, develop a methodology to purify stem cells from normal adult breast tissue, and derive information about their frequency and regulation. Considerable progress has been made in developing a stem cell assay in the first year of this grant. We have established conditions that allow human mammary tissue to be regenerated in subrenal xenografts in highly immunodeficient mice, starting with small innocula of dissociated human mammary cells. Furthermore, we have shown that measuring the number of progenitors present in xenografts after several weeks serves as a sensitive and objective readout for the presence of primitive stem-like cells among the transplanted cells, allowing this system to be used as a quantitative stem cell assay. Transplants of FACS-separated sub-populations show that these stem cells have a CD49fhigh EpCAM-low CD31-CD45- phenotype. These findings set the stage for further biological and molecular characterization studies of normal human mammary stem cells and their relationship to human breast cancer stem cells.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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