TRANSFECTION OF RAT DERMAL PAPILLA CELLS WITH A GENE ENCODING A TEMPERATURE-SENSITIVE POLYOMAVIRUS LARGE T-ANTIGEN GENERATES CELL-LINES RETAINING A DIFFERENTIATED PHENOTYPE

The dermal papilla is a discrete group of cells at the base of the hai r follicle and is implicated in controlling the hair growth cycle. Ear ly passage dermal papilla cells can induce hair growth in vivo, but, u pon further culturing, this property is lost. In order to study the ev ents occurring in hair induction, a representative dermal papilla cell line was required. We have transfected passage 1 rat vibrissa dermal papilla cells with a polyomavirus large T gene encoding a temperature- sensitive T antigen, and generated permanent cell lines in which the i mmortalizing function can be switched off by temperature shift. The ce lls established without crisis, resembled cells in the starting popula tion, and retained the aggregative properties of early passage dermal papilla cells. Growth studies were performed on the immortalized cell lines, which showed that transferring the cells to the restrictive tem perature for the large T gene product resulted in cell senescence or q uiescence, and changes in morphology. Implantation of cell pellets int o the ears of immunologically compatible rats showed that the immortal cells retained hair-inductive ability. Cytokines are believed to have an important role in the control of hair growth. The pattern of cytok ine gene expression in the immortal cell lines was compared with early passage dermal papilla cells and a non-hair-inducing dermal papilla c ell line, using reverse transcriptase-polymerase chain reaction. Epide rmal growth factor, tumour necrosis factor, and interleukin-la were de tected in the immortalized and non-hair-inducing dermal papilla cell l ines, but were absent in passage 2 dermal papilla cells. All other cyt okines examined were detected in all the cell types under study. These results demonstrate that the polyomavirus large T-tsa-immortalized de rmal papilla cell lines are very similar to passage 2 dermal papilla c ells and thus provide a good model for hair growth studies. Cytokine e xpression profiles indicate that the expression of several cytokines m ay be implicated in hair induction. Further studies are under way to i nvestigate the relationship between cytokine expression and the hair g rowth cycle.