Abstract
Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal. These mini-organs are maintained by two autonomous populations of skin stem cells. The fast-cycling, highly proliferative stem cells of the nail matrix (nail stem cells (NSCs)) predominantly replenish the nail plate. Furthermore, the slow-cycling population of the nail proximal fold (nail proximal fold stem cells (NPFSCs)) displays bifunctional properties by contributing to the peri-nail epidermis under the normal homeostasis and the nail structure upon injury. Here, we discuss nail mini-organ stem cells’ location and their role in skin and nail homeostasis and regeneration, emphasizing their importance to orchestrate the whole digit tip regeneration. Such endogenous regeneration capabilities are observed in rodents and primates. However, they are limited to the region adjacent to the nail’s proximal area, indicating the crucial role of nail mini-organ stem cells in digit restoration. Further, we explore the molecular characteristics of nail mini-organ stem cells and the critical role of the bone morphogenetic protein (BMP) and Wnt signaling pathways in homeostatic nail growth and digit restoration. Finally, we investigate the latest accomplishments in stimulating regenerative responses in regeneration-incompetent injuries. These pioneer results might open up new opportunities to overcome amputated mammalian digits and limbs’ regenerative failures in the future.
Highlights
Nails are highly keratinized skin appendages that exhibit continuous growth under physiological conditions and full regeneration upon removal
The structure begins at the eponychium, separating a thickened layer of skin epidermis from the nail organ, which firmly adheres to the nail plate and protects the area between the nail and epidermis from exposure to germs and contamination
Based on several loss-of-function studies, it was determined that endogenous regeneration of the mammalian digit tips fails in the absence of several signaling pathways, including bone morphogenetic protein (BMP), Wnt and growth factors secreted by the Schwann-lineage cells [15,21,50, 53,54,68,69]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The thin epithelium of NB consists of one or two layers of suprabasal postmitotic keratinocytes Both flat human NP and claw-shaped murine NP lie atop of the keratogenous zone (KZ) and the nail bed (NB) and are protected with eponychium at the nail root and the hyponychium underneath the distal end of the NP. Mouse NP encircles the distal phalanx from dorsal and lateral sides while leaving the exceptionally extended hyponychium uncovered (Figure 1) To both structures sharing major characteristics, most keratins’ expression patterns are similar in both human and mouse digits [3]. The results obtained from studies performed on mouse models might soon translate into a potential clinical setting in humans
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
