342 Human skin and its appendages regeneration in the large full-thickness xenografting model

Abstract

Most of the skin biology data obtained from a mouse model. However, studies of human skin have shown differences in the cell molecular signatures, the processes of physiological regeneration, wound healing, the development of diseases, etc. Human skin xenografting to immunodeficiency mice allows the most complex experiments to study normal and pathological processes, the search for methods of therapy for various diseases of human skin. The main limitation of this approach is the graft size. Most studies use partial-thickness xenografts without terminal hairs with excision of the dermal part along with adipose tissue while small punch biopsies or follicular units of human scalp skin are used to study the structure of hair follicles. The purpose of the study was to develop a xenografting model of a reasonably large full-thickness skin flap containing terminal hair follicles. The graft size was 15×5 mm. The skin was successfully engrafted, all skin structures including epidermis, dermis, blood vessels, hair follicles, sebaceous and sweat glands were preserved. The xenografting procedure is traumatic and promotes catagen induction. On day 32, we observed active proliferation of the graft tissue, a network of small vessels in the dermis and epidermal ridges at the junction of the graft with the recipient’s skin. On day 78, the xenograft was at the late stages of regeneration, there was a general decrease in proliferation with reconstruction of papillary and reticular dermis, and hair follicles morphology corresponded to the anagen stage. On day 110, visible growth of hair shafts above the skin surface was observed. Our data indicate that the homeostasis establishment in a 15×5 mm full-thickness skin xenograft with terminal hair follicles is longer than that in a split-thickness skin graft and takes more than 12 weeks. The described humanized skin model is suitable for studying the regeneration of skin and its appendages with surrounding tissues.