First Steps Towards the Engineering of Genital Skin
Purpose The reconstruction male genital malformations is often limited by the lack of available skin. Genital skin growth is androgen-dependent, and the androgen receptor (AR) can be demonstrated in genital skin fibroblasts. A genital skin substitute should also exhibit a responsive AR. We seeded an Integra ®- matrix with genital skin fibroblasts and tested it for responsiveness to dihydrotestosterone (DHT) stimulation by measuring AR receptor expression. Because very few androgen-dependent genes have been identified, we also screened for AR-responsive genes. Material and Methods Genital skin fibroblasts were derived from the foreskin of 11 healthy boys. Cells were cultured in plastic flasks or on an Integra®-matrix. Following stimulation with DHT, AR-expression was evaluated by immunohistochemistry and western-blotting. Screening for potentially androgen-dependent genes was done by cDNA-chip array and RT-PCR. Results Genital skin fibroblasts cultured on an Integra® matrix showed enhanced AR-expression after DHT stimulation. Screening for potentially androgen regulated genes identified the IGFs-2- gene and the ApoD-gene as new candidates. Conclusions Seeding of an Integra®-matrix with genital skin fibroblasts is a useful first step towards a genital skin substitute. DHT-responsiveness is maintained, offering the potential for adequate growth at puberty. Our cell matrix system is also a useful experimental model, offering the potential to identify new androgen dependent genes.