085 Integrin blockers stimulate hair growth in microdissected human anagen VI follicles but not in murine skin organ culture.

Sven Müller-Röver1, Eva MJ Peters1, Ingrid Moll1, Michael P. Philpott2, Ralf Paus1. 1Dept. of Dermatology, University Hospital Eppendorf, University of Hamburg, Hamburg, Germany; 2Dept. of Dermatology, Queen Mary and Westfield College, London, UK

Integrins have been shown to play major roles during hair follicle morphogenesis. Therefore, the use of modulators of integrin binding may be a promising strategy for hair growth manipulation. Here, we have investigated the spatiotemporal distribution of the integrin chains a1, a2, a3, a4, a5, a6, and ß1 during murine hair follicle morphogenesis and hair follicle cycling in C57BL/6J mice, and have analysed the effect of functional integrin blockers such as anti-ß1 integrin antibodies, RGD peptides or disintegrins (echistatin, flavoridin, kistrin) on neonatal hair follicle morphogenesis in murine skin organ culture or adult human hair growth in vitro (microdissected anagen VI scalp hair follicles). During murine hair follicle morphogenesis, the beta-1 integrin chain is broadly expressed throughout skin, including in basal layer epidermal keratinocytes, developing hair buds and outer root sheath (ORS) as well as in fibroblasts of the dermal papilla (DP) and the perifollicular connective tissue sheath (CTS). a1 and a3 IR was found on sebocytes as well as on ORS and basal layer epidermal keratinocytes. a2 IR was mainly found on the CTS during catagen. a4 IR was found on nerve fibres and endothelial cells as well as on the most proximal hair matrix. a5 IR was detected, throughout the hair cycle, on DP and CTS fibroblasts, while a6 IR was found on all epidermal and distal ORS keratinocytes. Inhibitors of integrin binding such as RGD peptides or disintegrins did not alter significantly the velocity of hair follicle morphogenesis in murine skin organ culture of neonatal mouse skin biopsies (P1). In contrast, the functional inhibition of integrin binding promoted human hair growth in vitro: Microdissected human anagen VI hair follicles displayed significantly more hair shaft elongation compared to vehicle controls after administration of anti-ß1 integrin antibodies (p<0.005), RGD peptides (p<0.02) or the disintegrin echistatin (p<0.05). These results suggest that integrin signalling is an intriguing novel target for pharmaceutical hair growth modulation.