Therapeutic potential of stem cells in skin repair and regeneration

Stem cells are defined by their capacity of self-renewal and multilineage differentiation, which make them uniquely situated to treat a broad spectrum of human diseases. Based on a series of remarkable studies in several fields of regenerative medicine, their application is not too far from the clinical practice. Full-thickness burns and severe traumas can injure skin and its appendages, which protect animals from water loss. temperature change, radiation, trauma and infection. In adults, the normal outcome of repair of massive full-thickness burns is fibrosis and scarring without any appendages, such as hair follicles, sweat and sebaceous glands. Perfect skin regeneration has been considered im-possible due to the limited regenerative capacity of epider- mal keratinocytes, which are generally thought to be the key source of the epidermis and skin appendages. Currently, researches on stem cells, such as epidermal stem cells, dermal stem cells, mesenchymal stem cells from bone marrow, and embryonic stem cells, bring promise to functional repair of skin after severe burn injury, namely, complete regeneration of skin and its appendages. In this study, we present an overview of the most recent advances in skin repair and regeneration by using stem cells.

Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands

Background Patients with severe full-thickness burn injury suffer from their inability to maintain body temperature through perspiration because the complete destructed sweat glands can not be regenerated. Bone marrow-derived mesenchymal stem cells （BM-MSCs） represent an ideal stem-cell source for cell therapy because of their easy purification and multipotency. In this study, we attempted to induce human BM-MSCs to differentiate into sweat gland cells for sweat gland regeneration through ectodysplasin （EDA） gene transfection. Methods The dynamic expression of EDA and EDA receptor （EDAR） were firstly observed in the sweat gland formation during embryological development. After transfection with EDA expression vector, human BM-MSCs were transplanted into the injured areas of burn animal models. The regeneration of sweat glands was identified by perspiration test and immunohistochemical analysis. Results Endogenous expression of EDA and EDAR correlated with sweat gland development in human fetal skin. After EDA transfection, BM-MSC acquired a sweat-gland-cell phenotype, evidenced by their expression of sweat gland markers by flow cytometry analysis. Immunohistochemical staining revealed a markedly contribution of EDA-transfected BM-MSCs to the regeneration of sweat glands in the scalded paws. Positive rate for perspiration test for the paws treated with EDA-transfected BM-MSCs was significantly higher than those treated with BM-MSCs or EDA expression vector （P 〈0.05）. Conclusions Our results confirmed the important role of EDA in the development of sweat gland. BM-MSCs transfected with EDA significantly improved the sweat-gland regeneration. This study suggests the potential application of EDA-modified MSCs for the repair and regeneration of injured skin and its appendages.

Thermal injuries induce gene expression of endogenous c-fos,c-myc and bFGF in burned tissues

To investigate the expression sequence and distribution characteristics of the p rotooncogenes c fos, c myc and endogenous basic fibroblast growth factor (bFGF ) genes in burned tissues, and to explore the possible effects of changes in the se genes' functions on wound healing Methods Partial thickness burns of 30% TBSA were established on backs of Wistar rats In situ hybridization and histological methods were used to detect expression of c fos, c myc and bFGF genes in normal and burned tissue at 3 h, 6 h, 1 d, 3 d , 7 d and 14 d postburn Results Although expression of c fos and c myc genes and bFGF gene could be found in n ormal skin, the expression of all three were markedly induced by burn wounds and the expression models in sequence and distribution were quite different Expre ssion of c fos gene increased and peaked at 6 h Signals were mainly localiz ed in both nuclei of dermal fibroblasts and monocytes The expression of bFGF gene increased at 6 h and peaked at 1 d postburn, and was distributed in the cyt oplasm of fibroblasts C myc gene peaked 3 d postburn and was also distributed in the cytoplasm of fibroblasts Conclusions These results indicated that thermal injury could induce the expression of c fo s, c myc and bFGF at gene level, showing phasic control and regional distributi on The phasic expression of these genes suggests that there is an interaction between protooncogenes and bFGF, which may play an important role in wound heali ng The different expressions of c fos and c myc play an inducing role in reg ulating bFGF, and in turn affect wound healing

Umbilical cord-derived mesenchymal stem cells:strategies,challenges,and potential for cutaneous regeneration

Umbilical cord mesenchymal stem cells(MSCs)are a unique,accessible,and non-controversial source of early stem cells that can be readily manipulated.As the most common pluripotent cell,bone marrow-derived MSCs display limitations with the progress of stem cell therapy.By contrast,umbilical cord-derived cells,which have plentiful resources,are more accessible.However,several uncertain aspects,such as the effect of donor selection or culture conditions,long-term therapeutic effects,product consistency,and potential tumorigenicity,are the bottleneck in this clinical therapy.MSCs are predicted to undergo an unprecedented development in clinical treatment when a generally acknowledged criterion emerges.In the current paper,we highlight the application of umbilical cord-derived MSCs in skin therapies based on our previous studies,as well as the achievements of our peers in this field.This paper focuses on the strategies,challenges,and potential of this novel therapy.

ISCHEMIA AND REPERFUSION REDUCE THE ENDOGENOUS BASIC FIBROBLAST GROWTH FACTOR (bF GF) IN RATSKELETAL MUSCLES

Polyclonal antibodies directed against human recombinant basic fibroblast growth factor (bFGF) were used in immunohistochemical studies to localize this growth factor in normal and wounded rat skeletal muscles. bFGF immunoreactivity was found mainly in the extracellular matrix, primarily in the endomysium, including the heparin-containing basal lamina and also in the capillary basal membrane of both normal and wounded muscles, however the signal intensity was much stronger in normal muscles. After 4-hour ischemia, about 40% of skeletal muscle fibers lost their bFGF immunoreactivity. Muscles which experienced 4-hour ischemia and 24 reperfusion had only a weaker bFGF immunoreactivity. The pathological results supported the concept of destroyed cell connection and fiber necrosis in ischemia and reperfused muscles. The mechanisms involved in this reduced concentration of bFGF in wounded muscles included oxygen radical activation, inflammatory response and reduced secretion of endogenous bFGF. These results were only partially compatible with the established mitogenic role of this protein and suggested that a reduction of endogenous FGF may partly contribute to a delay in wound healing.