Aging Alters Functionally Human Dermal Papillary Fibroblasts but Not Reticular Fibroblasts: A New View of Skin Morphogenesis and Aging

Understanding the contribution of the dermis in skin aging is a key question, since this tissue is particularly important for skin integrity, and because its properties can affect the epidermis. Characteristics of matched pairs of dermal papillary and reticular fibroblasts (Fp and Fr) were investigated throughout aging, comparing morphology, secretion of cytokines, MMPs/TIMPs, growth potential, and interaction with epidermal keratinocytes. We observed that Fp populations were characterized by a higher proportion of small cells with low granularity and a higher growth potential than Fr populations. However, these differences became less marked with increasing age of donors. Aging was also associated with changes in the secretion activity of both Fp and Fr. Using a reconstructed skin model, we evidenced that Fp and Fr cells do not possess equivalent capacities to sustain keratinopoiesis. Comparing Fp and Fr from young donors, we noticed that dermal equivalents containing Fp were more potent to promote epidermal morphogenesis than those containing Fr. These data emphasize the complexity of dermal fibroblast biology and document the specific functional properties of Fp and Fr. Our results suggest a new model of skin aging in which marked alterations of Fp may affect the histological characteristics of skin

Hair follicle dermal sheath cells: unsung participants in wound healing

The dermal sheath that surrounds the outside of the hair follicle contains progenitor cells that maintain and regenerate the dermal papilla, a key component for hair growth. Our contention is that dermal sheath cells have other roles. We believe that they can become wound healing fibroblasts and perform an important function in the repair of skin dermis after injury. The dermal sheath has close developmental and anatomical parallels with follicle outer root sheath, the epithelial component that contains the stem cells responsible for replacing skin epidermis. Dermal sheath cells also have a myofibroblast or wound healing phenotype, and in animals with high follicle densities differences in wound healing are observed in conjunction with changes in the hair growth cycle. Similarly, in human beings there are apparent differences in wound healing responses between hairy and non-hairy body sites. Moreover, clinical and experimental data suggest that the involvement of follicle-derived dermal cells results in qualitatively improved dermal repair. Therefore, in a therapeutic context, hair follicle dermal cells provide an accessible option for the creation of dermal or full skin equivalents that could both improve wound healing and reduce scarring. Indeed, given the inductive properties of adult hair follicle dermal cells, it is reasonable to envisage a tissue engineering approach for the production of a skin equivalent that will grow hair follicles when grafted

Cellular and developmental aspects of androgenetic alopecia

The hair follicle is a highly complex system that can be investigated at many levels and from multiple perspectives, However, underlying the cyclic production of all hair fibres are a set of common developmental processes. Many current investigations of androgenetic alopecia concentrate on the direct influences of hormones on hair follicles at the cellular or intracellular level. This paper attempts to step back from this and consider the process of terminal to vellus transition in androgenetic alopecia in terms of basic cellular and developmental mechanisms. Ideas about the mechanism and timing of follicle size reduction are put forward, but the paper also tries to point out inherent difficulties in the investigation of androgenetic alopecia and important gaps in current knowledge

Hair follicle dermal cells differentiate into adipogenic and osteogenic lineages

The adult hair follicle dermal papilla (DP) and dermal sheath (DS) cells are developmentally active cell populations with a proven role in adult hair follicle-cycling activity and unique inductive powers. In stem cell biology, the hair follicle epithelium has recently been the subject of a great deal of investigation, but up to now, the follicle dermis has been largely overlooked as a source of stem cells. Following the sporadic appearance of muscle, lipid and bone-type cells in discretely isolated follicle DP and DS cell primary cultures, we demonstrated that cultured papilla and sheath cell lines were capable of being directed to lipid and bone differentiation. Subsequently, for the first time, we produced clonal DP and DS lines that had extended proliferative capabilities. Dye exclusion has been reported to be an identifying feature of stem cells; therefore, clonal papilla and sheath lines with differing capacity to exclude rhodamine123 were cultured in medium known to induce adipocyte and osteocyte differentiation. Both DS- and DP-derived clones showed the capacity to make lipid and to produce calcified material; however, different clones had varied behaviour and there was no obvious correlation between their stem cell capabilities and dye exclusion or selected gene expression markers. As a highly accessible source, capable of being discretely isolated, the follicle has important potential as a stem cell source for tissue engineering and cell therapy purposes. It will also be interesting to compare follicle dermal stem cell properties with the broader stem cell capabilities discovered in skin dermis and investigate whether, as we believe, the follicle is a key dermal stem cell niche. Finally, the discovery of stem cells in the dermis may have implications for certain pathologies in which abnormal differentiation occurs in the skin