NCE

An important feature of adult stem cells is the ability to bypass negative growth signals and participate in wound healing. Based on this premise, we identified a small subpopulation of human breast epithelial cells that is capable of bypassing negative growth signals. We identified a differential expression of genes that allowed for the rapid isolation of this novel somatic cell population from fresh disease-free human breast tissue. Importantly, this cell population is characterized by the over-expression of Bmi-1, a protein that plays an essential role in the self-renewal of stem cells and represses the cell cycle inhibitor, p16. This population of cells is therefore poised to express pluripotency markers at a level similar to that measured in human embryonic stem cells. It has the ability to self-renew and can express phenotypes of any of the three mammary lineages in vitro using cell culture differentiation assays. Importantly, these cells are also functional in vivo as observed after implantation in mice. Indeed, these human cells can differentiate into functional mammary outgrowths of human origin in the host mouse as we could document secretion of human milk in mice transplanted with these human somatic cells. We are currently investigating whether these cells can also differentiate into other lineages (tissue types) when cultured in the appropriate conditions. Our preliminary studies support that these cells will hold great promise in regenerative medicine and cell replacement therapy and may help overcome some of the important ethical and technical roadblocks related to the use of human embryonic stem cells.