Gene transfer to epidermal stem cells: implications for tissue engineering.
The skin is an attractive target for gene therapy because it is easily accessible and shows great potential as an ectopic site for protein delivery in vivo. Genetically modified epidermal cells can be used to engineer three-dimensional skin substitutes, which when transplanted can act as in vivo 'bioreactors' for delivery of therapeutic proteins locally or systemically. Although some gene transfer technologies have the potential to afford permanent genetic modification, differentiation and eventual loss of genetically modified cells from the epidermis results in temporary transgene expression. Therefore, to achieve stable long-term gene expression, it is critical to deliver genes to epidermal stem cells, which possess unlimited growth potential and self-renewal capacity. This review discusses the recent advances in epidermal stem cell isolation, gene transfer and engineering of skin substitutes. Recent efforts that employ gene therapy and tissue engineering for the treatment of genetic diseases, chronic wounds and systemic disorders, such as leptin deficiency or diabetes, are reviewed. Finally, the use of gene-modified tissue-engineered skin as a biological model for understanding tissue development, wound healing and epithelial carcinogenesis is also discussed.
Andreadis
Stelios T
ST
University at Buffalo, Bioengineering Laboratory, Department of Chemical and Biological Engineering, State University of New York, Amherst, NY 14260, USA. sandread@eng.buffalo.edu
D000818:Animals; D002454:Cell Differentiation; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D012867:Skin / Q000166:cytology / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D014158:Transcription, Genetic; D019076:Transgenes; D014945:Wound Healing
D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins