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Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands
Authors:Cai Sa  Pan Yu  Han Bing  Sun Tong-zhu  Sheng Zhi-yong  Fu Xiao-bing
Institution:1. Department of Histology and Embryology, School of Medicine,Shenzhen University, Shenzhen, Guangdong 518060, China;Department of Physiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;Burns Institute, First Affiliated Hospital, Chinese People'sLiberation Army General Hospital, Trauma Center of Postgraduate Medical College, Beijing 100037, China
2. Research Center of Medical Sciences, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou,Guangdong 510080, China
3. Burns Institute, First Affiliated Hospital, Chinese People'sLiberation Army General Hospital, Trauma Center of Postgraduate Medical College, Beijing 100037, China
Abstract: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.
Keywords:bone marrow-derived mesenchymal stem cells  sweat gland  ectodysplasin  regeneration
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