The Characteristics Of Distribution, Proliferation And Differentiation Of Epidermal Stem Cells In Different Development Stages And Different Outcome Of Burn Wound Therapy In Human Skin

Objectives: Generally speaking, epidermis is a self-renewable tissue and epidermal stem cells in basal layer proliferate and differentiate according to a programmed law for substituting terminally differentiated cells in outward layer. Thus, epidermal stem cells are considered to play an important role in the skin regeneration. Also, they are considered the key resource for epidermis and skin appendages, such as hair follicles and sweat glands, etc.In normal epidermis, the histological studies showed that these epidermal stem cells are a single layer situated in the basement membrane of the epidermis or in the hair follicles and sweat glands. It is estimated that these cells comprise 1%~10% of the basal layer in vivo. According to their most salient features, namely slowly-cycling nature and high proliferative potential, they can be identified by in vivo and in vitro. In clinic, the postnatal cutaneous wounds caused by different kinds of wounds can not obtain complete regeneration for its anatomic structure and function. One of the main reasons is its mechanism of proliferation and differentiation of skin epidermal cells is still completely unknown. Moreover, the effective methods to regulate cell proliferation, differentiation and wound regeneration in clinic are lack.Recently, we have shown some interesting histological findings in the regenerated epidermis treated with recombinant human epidermal growth factor (rhEGF). In these regenerated epidermis, some new epidermal "stem cell islands" characterized by 1 integrin and K19positive staining were observed among the spinous and granular layer cells. Normally, in these sites there are only differentiated spinous and granular layer cells and undifferentiated stem cells are absent. These findings may offer the direct evidence for epidermal cell reversion from differentiated cells to undifferentiated stem cells in vivo and may be useful in exploring in depth the cellular and molecular mechanisms underlying the promotion of wound healing by rhEGF.A large and deep burn often heal with scar, and the thin epidermal layer, bad property of wear-resisting, preferential ulceration and no sweats often occur in scar tissue even in the late period of cicatrisation. The relationship between the disturbance of cell proliferation and differentiation of scar epidermal cells is not completely clear.In order to answer the biological questions presented from the previous research and the clinic investigation, the cellular surface markers for various differentiated phases in the course of differentiation of epidermal stem cells and immunohistochemical method are used to investigate the characteristics of distribution and amounts of epidermal stem cells and transit amplifying cells (TA cells) in normal skins from different development stages and scars from children and adult skins. The changes of epidermal cell proportion in skins derived from fetus with different embryonic gestational ages (EGA), children and adult were studied. So, the following two aims are hoped to achieve: One is to investigate the biological characteristics of proliferation and differentiation of epidermal stem cells in normal and scar tissues and the relationship between these characteristics and scar healing or scarless wound healing in order to-7-provide theoretical basis for the future anatomic structure and function repair of skin through epidermal stem cells fast proliferation; The other is to carry out an identification study about "stem cell islands" based on above results and new method in order to exclude error in methodology.Finally, we hope to establish a culture method for epidermal stem cells in vitro in order to provide the methodological basis for further study of the possibility of epidermal cell reversion induced by EGF and the intrinsic mechanisms controlling cell differentiation in wound regeneration.Methods: The skins of fetus were taken from the back of spontaneously aborted fetus because of trauma. The normal skin a...