Hair-follicle-associated pluripotent (HAP) stem-cell-sheet implantation accelerates cutaneous wound closure and suppresses scar formation in a mouse model

Patients frequently experience physical, mental, and even financial distress because of acute or chronic skin wounds. In severe situations, scarring on the skin can be quite noticeable, cause persistent discomfort, restrict joint motion, or be mentally taxing. Hair-follicle-associated pluripotent (HAP) stem cells were discovered by our laboratory, in the bulge area of the hair follicle and can differentiate to neurons, glia, beating cardiomyocytes, keratinocytes and nascent vessels. In the present study, HAP stem cell sheets were formed by culturing the upper part of hair follicles and implanting into mice with skin ulcers. The HAP stem cell sheets contained keratinocytes, endothelial cells and neurons. Autologous HAP stem cell sheet implantation to the dorsal wound in C57BL/6J mice significantly accelerated wound closure compared with non-implanted control mice. HAP-stem-cell sheets expressing green fluorescent protein (GFP) implanted into nude mice differentiated into keratinocytes in the epidermis, and neurons and endothelial cells in the dermis. The thicknesses of the epidermis and dermis and M2 macrophage and myofibroblast infiltration into the wound were significantly decreased in HAP-stem cell-implanted mice compared with non-implanted control mice. Expression levels of TGF-β1, COL1A2 and COL3A1 mRNA in the wound were significantly decreased in HAP stem cell-implanted mice compared with non-implanted control mice. These results suggest that implanting HAP stem cell sheets accelerates cutaneous wound closure and suppresses scar formation. The HAP stem cells used in the present study thus have potential as a future clinical strategy for accelerating wound healing.