IN-VIVO REGULATION OF MURINE HAIR-GROWTH - INSIGHTS FROM GRAFTING DEFINED CELL-POPULATIONS ONTO NUDE-MICE

The nude mouse graft model for testing the hair-forming ability of sel ected cell populations has considerable potential for providing insigh ts into factors that are important for hair follicle development and p roper hair formation. We have developed a minimal component system con sisting of immature hair follicle buds from newborn pigmented C57BL/6 mice and adenovirus E1A-immortalized rat vibrissa dermal papilla cells . Hair follicle buds contribute to formation of hairless skin when gra fted alone or with Swiss 3T3 cells, but produce densely haired skin wh en grafted with a fresh dermal cell preparation. The fresh dermal cell preparation represents the single cell fraction after hair follicles have been removed from a collagenase digest of newborn mouse dermis. I t provides dermal papilla cells, fibroblasts, and possibly other impor tant growth factor-producing cell types. Rat vibrissa dermal papilla c ells supported dense hair growth at early passage in culture but progr essively lost this potential during repeated passage in culture. Of 19 E1A-immortalized, clonally derived rat vibrissa dermal papilla cell l ines, the four most positive clones supported hair growth to the exten t of approximately 200 to 300 hairs per 1-2 cm2 graft area. The remain ing clones were moderately positive (five clones), weakly positive (th ree clones), or negative (seven clones). Swiss 3T3 cells prevented con traction of the graft area but did not appear to affect the number of hairs in the graft site produced by dermal papilla cells plus hair fol licle buds alone. The relatively low hair density (estimated 1-5% of n ormal) resulting from grafts of hair follicle buds with the most posit ive of the immortalized dermal papilla cell clones compared to fresh d ermal cells suggests that optimal reconstitution of hair growth requir es some function of dermal papilla cells partially lost during the imm ortalization process and possibly the contribution of other cell types present in the fresh dermal cell preparation, which is not supplied b y the Swiss 3T3 cells. The current graft system, comprising hair folli cle buds and immortalized dermal papilla cell clones, provides an assa y for positive or negative influences on hair growth exerted by added selected cell types, growth factors, or other substances. Characteriza tion of the phenotype of the dermal papilla cell lines, which differ i n their ability to support hair growth when grafted with hair follicle buds, may provide insight into specific dermal papilla cell propertie s important for their function in this system.