Cellular and extracellular involvement in the regeneration of the rat lower vibrissa follicle

Abstract

The sequence of events leading to the reconstruction of a fibre-producing hair follicle, after microsurgical amputation of the lower follicle bulb, has been detailed by immunohistology and electron microscopy. The initial response was essentially found to be a wound reaction, in that hyperproliferative follicle epidermis quickly spread to below the level of amputation—associated with downward movement of mesenchymal (or dermal) sheath cells. Fibronectin was prominent in both dermis and epidermis at this stage and, as in wound repair, preceded laminin and type IV collagen in covering the lower dermal-epidermal junction. Once a new basal line of epidermis and a complete basement membrane were established, laminin and type IV collagen were detected below this junction and within the prospective papilla-forming mesenchyme. This coincided with ultrastructural observations of profuse sub-basement membrane extracellular material in the region of new papilla formation. The glassy membrane displayed extensive ultrastructural modifications at its lower level, and these corresponded with localized variations in staining intensities for all three antibodies over time. The membrane hung below the level of the epidermis, and was crossed by migrating cells from the mesenchymal dermal sheath of the follicle - it acted to segregate the inner group of follicular dermal cells from wound fibroblasts. Extracellular matrix may be a mediator of the dermal-epidermal interactions associated with this hair follicle regeneration phenomenon.

Mesenchyme governs hair follicle induction

“…Later, tissue recombination of hair-forming dorsal mesenchyme with the glabrous plantar epithelium revealed that the inductive capacity resides in the dorsal skin mesenchyme as early as the DC forms (Kollar, 1970). These and other studies have established that the hair follicle dermal component, the DP and its precursor the DC, contain the capacity to induce de novo hair follicle formation in the skin, as well as other epithelial tissue of ectodermal origin, such as dental and corneal epithelia (Oliver, 1970;Kollar, 1970;Hardy, 1992;Ferraris et al, 2000;Dhouailly, 1973;Cohen, 1961;Kollar & Baird, 1970;Higgins et al, 2013;Jahoda et al, 1992). The extrapolation of these findings has established the current paradigm, which posits that the mesenchyme is the site of the hair-inductive signal.…”

Understanding Mammalian Hair Follicle Ecosystems by Single-Cell RNA Sequencing

“…Rahmani et al [ 44 ] found that DS contains a self-renewing cell population that is kept in the territory of mesenchymal niche in successive hair follicle cycles, and at the beginning of anagen, HFSCs will regenerate a new DS and repopulate the DS and the DP with new cells. When the hair follicle root was removed, DS was involved in the repair of DP [ 45 ].…”

“…The DS cells further migrated into the glass membrane and entered the extracted hair stem cavity. The new DP was formed and gradually expanded, and the hair fibers began to form [ 45 ]. Therefore, cell-based therapy using DS cells to enhance hair regeneration potential is an appealing possibility.…”

Epidermal stem cells

“…There is also some evidence for a reservoir of stem cells within the bulb of the hair follicle (24,25,29). Many authors discount the latter region as a possible stem cell reservoir because follicular regeneration is still observed after removal of the lower hair follicle as long as there is a dermal papilla close by (30)(31)(32)(33)(34)(35). However, it is possible that in homeostatic circumstances these deeply protected cells play a role in at least follicular maintenance.…”