Toshikazu Kamiya

Topical application of cyclosporin A induces rapid-remodeling of damaged anagen hair follicles produced in cyclophosphamide administered mice

Adult C3H mice which had either anagen IV or anagen VI hair follicles were given the anti-tumor drug cyclophosphamide, and cyclosporin A or minoxidil were topically applied to the mice daily from the 4th day after cyclophosphamide administration. In the mice that had anagen IV-hair follicles, 0.5% cyclosporin A induced very thick and long hairs after 21 days of cyclophosphamide administration, while vehicle and 1% minoxidil induced sparsely visible, short hairs. In the mice which received cyclosporin A, the injured hair follicles seemed to remodel themselves into intact anagen hair follicles and restart the production of hairs, instead of shifting to telogen. In the mice that had anagen VI-hair follicles at the time of cyclophosphamide administration, complete alopecia occurred within the first 7 days in all groups. After 14 days of cyclophosphamide administration, hair regrowth was observed in both the 0.5% cyclosporin A-group and the 1% minoxidil- group with the predominant effect over the vehicle. This study shows that anagen hair follicles respond to cyclophosphamide in different ways depending on their stages (IV and VI), and that the damaged anagen IV hair follicles have the potential of remodeling themselves, which is promoted by topical cyclosporin A administration.

HAIR FOLLICLE ELONGATION IN ORGAN CULTURE OF SKIN FROM NEWBORN AND ADULT MICE

By means of skin organ culture, some biological characteristics of hair follicle elongation were examined. When skin sections from 6-day-old C3H mice were cultured, spontaneous elongation of hair follicles was maintained. Without insulin, hair follicle elongation was poorly maintained irrespective of the presence of serum at 20%. Insulin could be replaced by IGF-I at 100 ng/ml. During in vitro elongation of hair follicles, bromodeoxyuridine was incorporated into germinal epithelial cells around dermal papillae. Skin sections from 4-week-old C3H mice did not show hair follicle elongation in complete medium. However, when 0.5 mM minoxidil was added to the medium, concentration dependent thickening and elongation of hair follicles was observed. In contrast, in vitro elongation of newborn pelage hair follicles was not enhanced by minoxidil. These results suggest that this system with the use of skin sections from 4-week-old C3H mice would be a potential in vitro model of human androgenic alopecia in which the anagen phase is suppressed but the suppression is partially released by minoxidil.

KF19418, a new compound for hair growth promotion in vitro and in vivo mouse models

KF19418, a newly synthesized compound, stimulated proliferation of cultured hair bulb cells from new born mice in concentration-dependent manner in the range under 10 microM. In the culture system of whole skin pieces from 4-week-old mice which we earlier established, KF19418 promoted hair follicle elongation as in the case of minoxidil. After topical application for 2 weeks of KF19418 or minoxidil to dorsal skin of hair-clipped mouse alopecia model, KF19418 at 1% suspension accelerated hair regrowth at a rate comparable to 1% minoxidil solution. Thus, it was shown that KF19418 directly stimulated hair follicle in vitro and had hair growth promoting activities in vivo.