Hair follicle stem cell-targeted gene transfer and reconstitution system.
Gene transfer to hair follicle (HF) epithelium is an attractive approach for not only treating skin diseases, but also many systemic disorders. In this study, we attempted to develop a gene transfer system for HF epithelial stem cells to maximize the beneficial therapeutic effects. For persistent and stable transgene expression in HF stem cells, we transferred retroviral vectors encoding reporter genes into cultured HF stem cells. In addition, these cells were mixed with cultured dermal papilla cells and transplanted on to immunodeficient mice. We succeeded in reconstituting HFs and their appendages in which these cells harbored a transgene reporter. The transgene expression was observed in all skin epithelial compartments including the HF epithelium, sebaceous gland and epidermis. In addition, transgene expression was observed for at least 6 months. This HF stem cell-targeted gene transfer and reconstitution system provides reliable gene-function analysis and gene therapy.
Sugiyama-Nakagiri
Y
Y
Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
Akiyama
M
M
Shimizu
H
H
D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D049452:Green Fluorescent Proteins / Q000235:genetics; D018859:Hair Follicle / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D008855:Microscopy, Electron, Scanning; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D012038:Regeneration; D012190:Retroviridae / Q000235:genetics; D012871:Skin Diseases / Q000628:therapy*; D013234:Stem Cells / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods*; D019076:Transgenes; D014738:Vibrissae; D001616:beta-Galactosidase / Q000235:genetics
D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase