人骨髓间充质干细胞转染外胚层发育不良素用于汗腺再生移植。
Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands.
机构信息
Department of Histology and Embryology, School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China.
出版信息
Chin Med J (Engl). 2011 Aug;124(15):2260-8.
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.
背景
严重全层烧伤的患者由于完全破坏的汗腺无法再生，无法通过出汗来维持体温，因此会遭受痛苦。骨髓间充质干细胞（BM-MSCs）因其易于纯化和多能性而成为细胞治疗的理想干细胞来源。在这项研究中，我们试图通过外胚层发育蛋白（EDA）基因转染诱导人 BM-MSCs 分化为汗腺细胞，以实现汗腺再生。
方法
首先观察 EDA 和 EDA 受体（EDAR）在胚胎发育过程中汗腺形成中的动态表达。转染 EDA 表达载体后，将人 BM-MSCs 移植到烧伤动物模型的损伤区域。通过发汗试验和免疫组织化学分析鉴定汗腺的再生。
结果
内源性 EDA 和 EDAR 的表达与人类胎儿皮肤中的汗腺发育相关。EDA 转染后，BM-MSC 获得了汗腺细胞表型，这一点通过流式细胞术分析证实了其表达的汗腺标志物。免疫组织化学染色显示 EDA 转染的 BM-MSCs 明显有助于烫伤足的汗腺再生。用 EDA 转染的 BM-MSCs 处理的足部发汗试验的阳性率明显高于用 BM-MSCs 或 EDA 表达载体处理的足部（P < 0.05）。
结论
我们的研究结果证实了 EDA 在汗腺发育中的重要作用。转染 EDA 的 BM-MSCs 显著改善了汗腺再生。这项研究表明 EDA 修饰的 MSC 具有修复和再生受损皮肤及其附属物的潜力。
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