Dermal papilla cells induce keratinocyte tubulogenesis in culture.

The ability of dermal papilla (DP) cells to induce hair growth was reported in many studies. However, early stages of hair follicle development and signals that govern this process are poorly understood. Therefore, an in vitro model may be a convenient system to study epithelial-mesenchymal interactions and early stages of epidermal morphogenesis, especially in humans. To investigate the role of DP cells in epidermal morphogenesis we modified the method of isolation of DP cells from hair follicle of human scalp and developed the three-dimensional model of epidermal morphogenesis. Isolated DP cells were able to differentiate in adipogenic and osteogenic directions and retained activity of alkaline phosphatase (AP) for seven passages in culture. DP cells were able to induce tubule-like structures in three-dimensional model in vitro and to reorganize collagen matrix. Prolonged cultivation of DP cells has been a big problem because of the loss of hair follicle-inducing ability and growth activity after several passages. To solve this problem we immortalized DP cells by the transfection of the human telomerase reverse transcriptase cDNA (hTERT). Immortalized DP-hTERT cells retained AP activity and demonstrated low ability to osteogenic differentiation. The conditioned medium collected from actively proliferated cells as well as DP-hTERT cells themselves were capable to induce tubulogenesis after prolonged keratinocyte cultivation.

Label retaining cells and cutaneous stem cells.

This is a comprehensive review on label retaining cells (LRC) in epidermal development and homeostasis. The precise in vivo identification and location of epidermal stem cells is a crucial issue in cutaneous biology. We discuss here the following problems: (1) Identification and location of LRC in the interfollicular epithelium and hair follicle; (2) The proliferative potential of LRC and their role in cutaneous homeostasis (3); LRC phenomenon and the Immortal Strand Hypothesis, which suggests an alternative mechanism for retention of genetic information; (4) Significance of LRC studies for development of stem cell concept. Now, it seems evident that LRC are a frequent feature of stem cell niches and revealing highly dormant LRC may be used for identification of stem cell niches in different tissues. LRC were used for screening specific markers of epidermal stem cells. Within a given tissue stem cells have different proliferative characteristics. There are more frequently cycling stem cells which function primarily in homeostasis, while LRC form a reserve of dormant, may be ultimate, stem cells, which are set aside for regeneration of injury or unforeseen need. The authors suggest that LRC dormancy described in Mammalia has much in common with developmental quiescence found in some other animals. For example in C. elegans reproductive system, vulval precursor cells have developmentally programmed cell-cycle arrest in the first larval stage, and then undergo an extended period of quiescence before resuming proliferation. Another example of developmental quiescence is the diapause, a widespread phenomenon exhibited by animals ranging from nematodes to mammals, often occurring at genetically predetermined life history stage.