Isolation and characterization of normal adult human epithelial pluripotent stem cells.
Both reproductive and therapeutic cloning of human stem cells have been made possible with recent technological advances in the isolation of embryonic stem cells and of pluripotent stem cells from adult tissues. We have isolated normal human kidney and human breast epithelial stem cells, as well as having characterized "immortalized" cells from human neuronal and human pancreatic tissue (Trosko et al., Methods 20:245-264, 2000). The isolation was motivated by the stem cell theory of carcinogenesis. Based on the assumption that stem cells would not express connexin genes, nor have functional gap junctional intercellular communication (GJIC), we have demonstrated that the human kidney, breast, neuronal, and pancreatic stem cells can divide either symmetrically or asymmetrically, depending on whether they are grown in microenvironmental conditions that suppress GJIC (the undifferentiated, proliferative state) or induce GJIC (the differentiated state). Normal breast epithelial stem cells appear to be intrinsically "immortal" until induced to express GJIC, at which time, with appropriate substrate and microenvironmental nutrients, they can form three-dimensional "organoids." expressing markers associated with the mature mammary tissue and forming a physical structure very similar to the in vivo budding, ductal structures. The breast stem cells can be prevented from "mortalizing" and can be converted to neoplastic cells, which maintain many phenotypes of the stem cells.
National Food Safety Toxicology Center, Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA. james.trosko@ht.msu.edu
James E
JE
Trosko
Chia-Cheng
CC
Chang
D000328:Adult; D001940:Breast / Q000166:cytology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002460:Cell Line; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002999:Clone Cells; D004847:Epithelial Cells / Q000166:cytology; D006801:Humans; D007668:Kidney / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology*