Original article from STEM CELLS
“Skin-derived Precursors as a Source of Progenitors for Cutaneous Nerve Regeneration”
Studies have taught us that while peripheral cutaneous nerves have an amazing regenerative capability in response to damage (Navarro et al), numerous human diseases are associated with incomplete nerve regeneration. Proliferating Schwann cells are key players in nerve regeneration by guiding axons towards their denervated targets (Webber and Zochodne) and secreting neurotrophins to support injured axons and prevent apoptosis (Tofaris et al). However, these Schwann cells lack the sustained growth ability needed for the production of glial cells; the non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons. It had been hypothesised that mature Schwann cells dedifferentiated into progenitor/stem-like cells to promote axonal regrowth following injury (Scherer and Salzer). However, the discovery of neural crest stem cells at sites of gliogenesis in the peripheral nervous system and neural crest-like stem cells in the skin (see original paper for references) suggests that resident adult stem cells may be the source of progenitors for cutaneous nerve regeneration. Two groups have published reports on the identification of skin-derived precursors/progenitors (SKPs); self-renewing, multipotent neural stem/precursor cells which are distinct from other known stem/precursor cells within the skin, which have the capacity to differentiate along neuronal and glial lineages (Toma et al, McKenzie et al and Li et al) and into glial cells in response to the nerve microenvironment within spinal cord and sciatic nerve injuries in mouse models (McKenzie et al, Biernaskie et al and Walsh et al). Now, in a study published in Stem Cells researchers from the laboratory of Lu Q. Le demonstrate that SKPs are a potential source of progenitors for cutaneous nerve regeneration and further show the critical role SKPs play in cutaneous nerve homeostasis through the use of in vivo and in vitro three-dimensional cutaneous nerve regeneration models (Chen and Pradhan et al).