Trigger Follicle Generation in Wounds
In 2007, Cotsarelis et al. at University of Pennsylvania discovered for the first time that it is possible to new hair follicles through activating epidermal stem cells in an adult mouse model. They reported that de novo generation of hair follicles is possible using wounding to activate stem cells in adult mice.
In this study, an epidermal tissue of 1.0-2.5cm in diameter was resected from the dorsum of adult mice. This activated stem cells in the wound and triggered molecular reactions similar to the fetal development which led to de novo generation of follicles and eventual hair growth. The skin showed changes similar to those during embryonic follicle generation. That is, the dormant embryonic molecular mechanism was activated through the induced wound and supplied stem cells.
Stem cells have the ability to differentiate into all types of cells. Stem cells that trigger follicle generation in wounds are different from those involved in embryonic follicle generation. Stem cells in the wound are not embryonic stem cells but have originated from epidermis. Epidermal cells may have been reprogrammed to become follicle stem cells.
Various follicle stem cells have so far been found to exist at the sebaceous gland, including epidermal stem cells, mesenchymal stem cells, and melanin stem cells.The follicle can be called a reservoir of stem cells.
Epidermal hair follicle stem cellsare involved in the continuous maintenance and remodeling of follicles. The epidermal follicle consists of many layers; hair shaft, inner root sheath, companion layer, and outer root sheath. These epidermal layers lie perpendicular to the follicle and can be divided into the bulb region, suprabulbar region, isthmus, infundibulum, and interfollicular epidermis(IFE). Isthmus lies between these baceous gland and APM and is of high anatomical importance has it houses the follicle stem cell niche. The hair shaft is synthesized in the precortical hair matrix which is the place of secondary hair germ(SHG) during the telogen phase.
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It is also the place for proliferation and differentiation of transit amplifying cells(TACs) into hair shaft in the anagen phase. Stem cell derived follicle cells are involved in creating the sebaceous gland which originates from the epidermis and ORS. In a mouse model, hair follicle stem cells were believed to regenerate wounded IFE. There is also clinical data that this occurs in humans as well. In humans, follicular epidermis contains melanin stem cells which is the source of follicular melanocytes and they can be found with MITF and PMEL17 expression. Unlike mouse follicle cells, Merkel cells in human ORS have their own epidermal stem cells. Connective tissue sheath(CTS) and dermal papilla(DP) originate from mesynchemal cells and are morphologically different from follicle epidermis. They have been found to contain pluripotent cells such as skin-derived precursor cells, Nestin+ cells or SOx2+cells. These stem cells are assumed to be extensively involved in generating dermal and follicle fat, blood vessels, connective tissues and glial cells.
TA Cell Population
Epithelial stem cells are thought to be slow cycle cells with potent proliferation. That is, in stem cell niche, stem cell progeny become transit amplifying(TA) cells and then turn into post mitotic cells when they lose pluripotency.
TA cell population include young TA cells with high pluripotency and more mature TA cells that lose pluripotency in a matter of a few hours. Reliable markers of epithelial stem cell are lacking and many studies used cellular dynamics to distinguish slow-cycling stem cells from faster cycling TA cells.To detect slow-cycling stem cells, tritiated thymidine(3H-T) or bromodeoxyuridine(BrdU) was continuously perfused to distinguish all differentiated cells.
Typically, TA cells with rapid cycling of 4-8 weeks get diluted and lose markers but slow-cycling stem cells retain the markers. These label-retaining cells(LRCs) can be detected by examination. When applying the labeling method to follicle, most LRCs were limited to the bulge.
-To be continued
