论文标题：Human induced pluripotent stem cell-derived vocal fold mucosa mimics development and responses to smoke exposure

期刊：Nature Communications

作者：Vlasta Lungova, Xia Chen, Ziyue Wang, Christina Kendziorski ,Susan L. Thibeault

发表时间：2019/09/24

数字识别码：10.1038/s41467-019-12069-w

微信链接：https://mp.weixin.qq.com/s/UNKB7L_N97uJWrlGr9HPjg

《自然-通讯》本周发表的一项研究Human induced pluripotent stem cell-derived vocal fold mucosa mimics development and responses to smoke exposure报道了人声带组织（即粘膜）的一个实验室三维模型。当暴露在香烟烟雾中时，该组织会出现在人喉中发现的反应，即炎症。该模型可用于对声带疾病或损害的相关药物和疗法研究。

图1：3D人声带组织（源于人诱导多能干细胞）的培养过程 图源: Lungova等

图2：组织在5%香烟烟雾提取物中暴露一周后的结构和功能基因表达变化 图源:Lungova等

声带不仅是我们发音的基础，也是分隔声道和食物饮料进入消化通道的关键分界，并能防止异物进入呼吸道。声带容易受到慢性炎症的影响，主要由环境损伤导致（包括香烟、过敏原或感染）。不过，由于从健康声带中提取细胞样本会导致不可逆的损伤，对声带疾病和修复策略的研究一直存在难度。

美国威斯康星大学麦迪逊分校的Susan Thibeault和同事在他们之前小鼠研究的基础上，从人诱导多能干细胞（hiPSC）中提取了声带上皮细胞。作者表明，hiPSC源性声带组织在遗传学和形态上都与天然人声带粘膜类似。作者随后将他们的组织在5%的香烟烟雾提取物中暴露了一周的时间，观察是否会诱导出与烟雾相关的粘膜炎症。结果显示，烟雾会导致粘膜炎症以及细胞类型的异常重塑，影响上皮屏障结构。

摘要：Development of treatments for vocal dysphonia has been inhibited by lack of human vocal fold (VF) mucosa models because of difficulty in procuring VF epithelial cells, epithelial cells’ limited proliferative capacity and absence of cell lines. Here we report development of engineered VF mucosae from hiPSC, transfected via TALEN constructs for green fluorescent protein, that mimic development of VF epithelial cells in utero. Modulation of FGF signaling achieves stratified squamous epithelium from definitive and anterior foregut derived cultures. Robust culturing of these cells on collagen-fibroblast constructs produces three-dimensional models comparable to in vivo VF mucosa. Furthermore, we demonstrate mucosal inflammation upon exposure of these constructs to 5% cigarette smoke extract. Upregulation of pro-inflammatory genes in epithelium and fibroblasts leads to aberrant VF mucosa remodeling. Collectively, our results demonstrate that hiPSC-derived VF mucosa is a versatile tool for future investigation of genetic and molecular mechanisms underlying epithelium-fibroblasts interactions in health and disease.

（来源：科学网）