Implanted hair-follicle-associated pluripotent (HAP) stem cells differentiating to keratinocytes, macrophages and endothelial cells accelerated cutaneous wound closure and suppressed scar formation in a mouse model

Abstract

Abstract BackgroundPatients frequently experience physical, mental, and even financial distress because of acute or chronic wounds to the skin. In severe situations, the skin scars 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 hair follicle; and can differentiate to neurons, glia, beating cardiomyocytes, keratinocyte and nascent vessel. In the present study, we determined if HAP stem cells can accelerate cutaneous wound healing in a mouse model.MethodsHAP stem cells which were grown from the upper part of vibrissa follicle and formed a sheet in culture were implanted to dorsal wounds in a mouse model. After HAP-stem-cell-sheet-implantation, progression of wound closure with time was evaluated. After wound closure, scar morphology, infiltration of dermal inflammatory cell such as macrophage and fibrocyte and dermal fibrosis were observed histologically. mRNA of TGF-β1, type I collagen alpha 2 (COL1A2) and type III　collagen alpha 1 (COL3A1) expression levels in the wound were measured by quantitative real-time PCR (RT-PCR) to assess dermal inflammation and fibrosis.ResultsHAP stem cells formed sheet which differentiated to keratinocytes, macrophages and endothelial cells in culture. After HAP-stem-cell-sheet-implantation to the dorsal wound in the mice model, it accelerated the wound closure, increased capillary-vessel-formation and suppressed macrophage and fibrocyte infiltration and collagen deposition in the dermis compared with non-implanted control mice. Also, mRNA of TGF-β1, COL1A2 and COL3A1 expression levels in the wound were decreased in the HAP-stem-cell-implanted mice compared with non-implantation control mice.ConclusionsImplantation of HAP stem cells differentiated to keratinocytes, macrophages and endothelial cells accelerated wound closure and suppressed scar formation in a mouse model, indicating clinical potential of scar-free wound healing.