Technical Report abstract


Nature Medicine 14, 1384 - 1389 (2008)
Published online: 23 November 2008 | doi:10.1038/nm.1791

A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability

Peter Eirew1, John Stingl1,6, Afshin Raouf1, Gulisa Turashvili2, Samuel Aparicio2,3, Joanne T Emerman4 & Connie J Eaves1,5


Previous studies have demonstrated that normal mouse mammary tissue contains a rare subset of mammary stem cells. We now describe a method for detecting an analogous subpopulation in normal human mammary tissue. Dissociated cells are suspended with fibroblasts in collagen gels, which are then implanted under the kidney capsule of hormone-treated immunodeficient mice. After 2–8 weeks, the gels contain bilayered mammary epithelial structures, including luminal and myoepithelial cells, their in vitro clonogenic progenitors and cells that produce similar structures in secondary transplants. The regenerated clonogenic progenitors provide an objective indicator of input mammary stem cell activity and allow the frequency and phenotype of these human mammary stem cells to be determined by limiting-dilution analysis. This new assay procedure sets the stage for investigations of mechanisms regulating normal human mammary stem cells (and possibly stem cells in other tissues) and their relationship to human cancer stem cell populations.

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  1. Terry Fox Laboratory, British Columbia Cancer Agency, 675 West Tenth Avenue, Vancouver, British Columbia V5Z 1L3, Canada
  2. Molecular Oncology and Breast Cancer Program, British Columbia Cancer Agency, 675 West Tenth Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
  3. Department of Pathology and Laboratory Medicine, University of British Columbia, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 2B5, Canada.
  4. Department of Cellular & Physiological Sciences, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
  5. Department of Medical Genetics, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.
  6. Present address: Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.

Correspondence to: Connie J Eaves1,5 e-mail: ceaves@bccrc.ca



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