The potential of nestin-expressing hair follicle stem cells in regenerative medicine.

The hair follicle bulge area is an abundant, easily accessible source of actively growing pluripotent adult stem cells. Nestin, a protein marker for neural stem cells, is also expressed in follicle stem cells and their immediate, differentiated progeny. Green fluorescent protein (GFP), whose expression is driven by the nestin regulatory element in transgenic mice, serves to mark hair follicle stem cells. The pluripotent nestin-driven GFP stem cells are positive for the stem cell marker CD34, but negative for keratinocyte marker keratin 15, suggesting their relatively undifferentiated state. These cells can differentiate into neurons, glia, keratinocytes, smooth muscle cells and melanocytes in vitro. In vivo studies show that nestin-driven GFP 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 a severed sciatic or tibial nerve greatly enhance the rate of nerve regeneration and the restoration of nerve function. 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 provide an effective, accessible, autologous source of stem cells for treatment of peripheral nerve injury.