The Hair Follicle Stem Cell as the Paradigm Multipotent Adult Stem Cell

Abstract

Our laboratory has discovered that the hair follicle is an abundant, easily accessible source of actively growing multipotent adult stem cells that can form non-follicular cell types. We observed that nestin, a protein marker for neural stem cells, is also expressed in follicle stem cells and their immediate, differentiated progeny. The green fluorescent protein (GFP), whose expression is driven by the nestin regulatory element in transgenic mice (ND-GFP mice), served to mark hair follicle stem cells and could be used to trace their fate. The ND-GFP hair-follicle stem cells are positive for the stem cell marker CD34 but negative for keratinocyte marker keratin 15, suggesting their relatively undifferentiated state. We have shown that these hair follicle stem cells can differentiate into neurons, glia, keratinocytes, smooth muscle cells and melanocvytes in vitro. In vivo studies show the hair follicle stem cells can differentiate into blood vessels and neural tissue after transplantation to the subcutis of nude mice. Hair follicle stem cells implanted into the gap region of severed sciatic or tibial nerves greatly enhance the rate of nerve regeneration and the restoration of nerve function. When transplanted to the severed nerves of the mice, the follicle cells transdifferentiate largely into Schwann cells, which are known to support neuron regrowth. The transplanted mice regain the ability to walk normally. Thus, hair follicle stem cells are multipotent and provide an effective, accessible, autologous source of stem cells for treatment of peripheral nerve injury and appear to be a paradigm for adult stem cells.