The Potential of Hair-Follicle-Associated Pluripotent (HAP) Stem Cells for Regenerative Medicine.

Abstract

Nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells from mouse and human have been shown to differentiate into neurons, glia, keratinocytes, smooth muscle cells, cardiac muscle cells, and melanocytes in vitro. HAP stem cells have promoted the recovery of peripheral nerve and spinal cord injuries in mouse models by differentiating into glial fibrillary acidic protein (GFAP)-positive Schwann cells. HAP stem cells enclosed on polyvinylidene fluoride membranes (PFM) were transplanted into the severed thoracic spinal cord of nude mice. After implantation, HAP stem cells differentiated into neurons and glial cells, which effected complete reattachment of the thoracic spinal cord.HAP stem cells were implanted into the injured brain of C57BL/6J or nude mice with induced intracerebral hemorrhage (ICH). After implantation, HAP stem cells differentiated into neurons, astrocytes, oligodendrocytes, and microglia in the ICH site, and demonstrated a significant functional improvement in mice. HAP-cell-sheets implanted on wounds in diabetic db/db mice effected wound healing. The levels of inflammation in the wound was suppressed by HAP-cell-sheet implantation. These results suggest autologous HAP stem cells can be used to heal refractory diabetic ulcers. HAP stem cells can differentiate into mature beating atrial and ventricular cardiomyocytes when cultured with specific supplements and have the potential for heart regeneration. HAP stem cells are readily obtained from scalp hair follicles, they do not develop teratomas and do not lose differentiation ability when cryopreserved. These results suggest that HAP stem cells have the potential as be a better source for regenerative medicine compared to induced pluripotent stem cells (iPS) or embryonic stem (ES) cells.