The major emphasis of several laboratories in epidermal biology is on developing gene therapy approaches for skin diseases. As in other fields, gene therapy in the skin has been hampered by the inability to target (or identify) a stem cell, and the lack of sustained gene expression. We instead asked whether we could identify an ectopic source of epithelial cells that could be induced into becoming a skin stem cell. Rather than searching for markers of the epidermal stem cell itself, we asked whether we could reprogram other epithelia into skin under the appropriate inductive (dermal) influences. Much work is currently focused on using the skin as a donor tissue of stem cells for other diseases (neurological, muscular), however, little interest is focused on how to induce other cell types to become skin. We reasoned that if the donor cells were taken from an immunologically-compatible individual or did not elicit an immune response, such cells could overcome the two major obstacles in gene therapy approaches: gene introduction and targeting the stem cell. Donor cells, by definition, would contain an intact gene-of interest, and importantly, others have shown that epidermal stem cells would be sequestered during the induction of the new skin and hair follicle, thus providing a lifelong supply of genetically corrected cells. The success of this project would represent the first demonstration of epithelial reprogramming in human tissues, and more significantly, provide a foundation for the clinical application of reprogrammed skin in the treatment of human genetic skin diseases.
