Wang Lu, Song Dongli, Wei Chuanyuan, Chen Cheng, Yang Yanwen, Deng Xinyi, Gu Jianying
Department of Plastic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
Zhongshan Hospital Institute for Clinical Science, Shanghai Institute of Clinical Bioinformatics, Shanghai Engineering Research for AI Technology for Cardiopulmonary Diseases, Shanghai Medical College, Fudan University, Shanghai, China.
J Transl Med. 2020 Feb 6;18(1):60. doi: 10.1186/s12967-020-02217-y.
Cell proliferation and death are key components of wound healing and tissue repair. Telocytes (TCs) represent a newly discovered cell type that can protect tissue from acute injury via cell-cell communication with adjacent cells. The aim of this study was to use a mouse model of skin wound healing and lipopolysaccharide (LPS)-induced cell injury to evaluate the effects of TCs on skin wound healing in vivo and in vitro.
MATERIAL/METHODS: Immunohistochemical staining was performed to evaluate the alteration of TCs in tissues from normal and chronic wound patients. Then, a male C57BL/6 mouse wound model of the back was established. The mice were divided randomly into three groups, and wound healing was estimated according to the wound healing rate and histology. An LPS-induced co-culture model of a mouse lung telocyte cell line (TCs) with human keratinocyte (HaCaT), human dermal microvascular endothelial cell (HDMEC) or murine fibroblast (L929) cell lines was established to analyse the effects of TCs on constitutive cell types of the skin. Cell proliferation, migration and apoptosis were examined, and reactive oxygen species (ROS) and inflammatory factors in HaCaT cells, HDMECs, and L929 cells were detected to study the mechanisms involved in TC protection in skin wounds.
TCs were significantly increased in tissues from chronic wound patients compared with healthy controls. Wound healing was significantly improved in wound mouse models treated with exogenous TCs compared with LPS-induced models. TCs reversed the LPS-induced inhibition of HaCaT cells and HDMECs and reduced the LPS-induced apoptosis of HaCaT cells and the death ratios of HDMECs and L929 cells. TCs reversed LPS-induced ROS in HDMECs and L929 cells and decreased inflammatory factor mRNA levels in HaCaT cells, HDMECs and L929 cells.
TCs reduce wound healing delay, and inflammatory responses caused by LPS might be mediated by inflammatory inhibition, thus restricting apoptosis and promoting migration of the main component cell types in the skin.
细胞增殖和死亡是伤口愈合和组织修复的关键组成部分。端粒细胞（TCs）是一种新发现的细胞类型，可通过与相邻细胞的细胞间通讯保护组织免受急性损伤。本研究的目的是使用皮肤伤口愈合小鼠模型和脂多糖（LPS）诱导的细胞损伤模型，在体内和体外评估端粒细胞对皮肤伤口愈合的影响。
材料/方法：采用免疫组织化学染色法评估正常和慢性伤口患者组织中端粒细胞的变化。然后，建立雄性C57BL/6小鼠背部伤口模型。将小鼠随机分为三组，根据伤口愈合率和组织学评估伤口愈合情况。建立LPS诱导的小鼠肺端粒细胞系（TCs）与人角质形成细胞（HaCaT）、人真皮微血管内皮细胞（HDMEC）或小鼠成纤维细胞（L929）细胞系的共培养模型，分析端粒细胞对皮肤组成细胞类型的影响。检测细胞增殖、迁移和凋亡情况，并检测HaCaT细胞、HDMECs和L929细胞中的活性氧（ROS）和炎症因子，以研究端粒细胞保护皮肤伤口的机制。
与健康对照相比，慢性伤口患者组织中端粒细胞显著增加。与LPS诱导的模型相比，外源性端粒细胞治疗的伤口小鼠模型的伤口愈合显著改善。端粒细胞逆转了LPS诱导的对HaCaT细胞和HDMECs的抑制作用，并降低了LPS诱导的HaCaT细胞凋亡以及HDMECs和L929细胞的死亡率。端粒细胞逆转了LPS诱导的HDMECs和L929细胞中的ROS，并降低了HaCaT细胞、HDMECs和L929细胞中的炎症因子mRNA水平。
端粒细胞减少伤口愈合延迟，LPS引起的炎症反应可能通过炎症抑制介导，从而限制细胞凋亡并促进皮肤主要组成细胞类型的迁移。
