082 Balding Scalp Dermal Papilla Cells Secrete a Soluble Factor(s) Which Delays the Onset of Anagen in Mice in vivo

K. Hamada1 and V. A. Randall2. Basic Research Laboratory, Kanebo Ltd., Kanagawa, Japan1 and Dept. of Biomedical Sciences, University of Bradford, West Yorkshire, UK2

Androgens are required for scalp hair follicle miniaturisation in androgenetic alopecia, but their mechanism of action is unclear. The mesenchyme-derived dermal papilla is probably the key tissue in androgenic regulation. Cultured dermal papilla cells secrete soluble factors which stimulate the growth of other follicular cells. Our earlier studies demonstrated that media conditioned by balding dermal papilla cells had less stimulatory capacity for either human or rat cultured dermal papilla cells than normal scalp cell media. This study was designed to determine whether balding or normal scalp cell media affected mouse hair growth in vivo. Conditioned media from dermal papilla cells derived from normal, balding and clinically normal androgenetic alopecia scalp follicles (24h in serum-free medium) were injected subcutaneously into the shaved backs of C3H/HeN mice (n=5 or 6; injections days 1, 3, 4, 6). After 65 days, hair growth was assessed visually, by histology and by quantitating hair cycle markers. Normal cell media had no effect, but hair growth was delayed in mice treated with balding or clinically normal balding cell conditioned media compared to both control serum-free media and normal cell media. Histological examination confirmed the anagen and telogen definition by observation and revealed no pathological changes in follicles from conditioned media treated mice. Analysis of cell proliferation (gamma- glutamyl transpeptidase) and angiogenesis (alkaline phosphatase) markers confirmed that hair growth was present in 4/6 control mice and 4/5 treated with normal cell media, but only 1/6 treated with balding and 2/5 with clinically normal balding cell media. Thus, androgenetic alopecia dermal papilla cells from both balding and almost normal follicles clinically appear to be secreting soluble factor(s) into their media which can delay the onset of anagen in mice in vivo. Such factors were not present in normal scalp cell media as this had no effect on mouse hair growth in vivo. This inhibitory factor(s) appears to act across species. Such anagen-delaying or telogenprolonging paracrine factors may well be important in the processes of androgenetic alopecia.