Hair Follicle Pluripotent Stem (hfPS) Cells

Abstract

Our laboratory has discovered that nestin, a protein marker for neural stem cells is also expressed in hair follicle stem cells and their immediate, differentiated progeny. The 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 enabled us to make this observation. 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 melanocytes 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 severed nerves in 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. We have also shown that hair follicle stem cells can affect the functional joining of the severed spinal cord. When the hair follicle stem cells are injected into the severed spinal cord, they differentiate into Schwann cells enabling the cord to rejoin and the mouse to regain function of its rear legs. Thus, hair follicle pluripotent stem (hfPS) cells can 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.