Alveolar Differentiation Potency of Human Distal Airway Stem Cells Is Associated with Pulmonary Pathological Conditions
Alveolar Differentiation Potency of Human Distal Airway Stem Cells Is Associated with Pulmonary Pathological Conditions
复制标题
人远端气道干细胞的肺泡分化能力与肺部病理状况相关
DOI：
10.1155/2019/7123078
复制
发表时间：
2019-01-01
影响因子：
4.3
通讯作者：
Zuo, Wei
中科院分区：
文献类型：
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作者：
Wang, Yujia;Lu, Yi;Zuo, Wei
背景本研究旨在鉴定人远端气道干细胞（DASC）并评估其在慢性退行性肺病患者中的治疗潜力。这些发现将为利用自体气道干细胞作为呼吸系统疾病的治疗干预的进一步临床应用提供全面的理解。方法从健康受试者或诊断为支气管扩张、慢性阻塞性肺疾病（COPD）或间质性肺疾病（ILD）的患者中分离DASC。分化能力，干细胞的一个关键属性，使用一种新的单层分化系统进行了研究。评估分化细胞的肺泡和支气管细胞标志物表达，并进一步检查分化细胞的定量表达水平与受试者年龄和肺功能的关系。结果与结论DASC和TSCs分化为肺泡样结构和管状结构，具有不同的标记基因表达。此外，单细胞衍生的克隆显示出不同的分化命运，即使克隆来自相同或不同的个体。更重要的是，患者来源的DASC的肺泡分化潜能高于健康人。在支气管扩张和ILD患者中，DASC的分化效率也与年龄相关。
Background This study is aimed at characterizing the human distal airway stem cells (DASCs) and assessing their therapeutic potential in patients with chronic, degenerative lung diseases. These findings will provide a comprehensive understanding for further clinical applications utilizing autologous airway stem cells as therapeutic intervention in respiratory diseases. Methods DASCs were isolated from healthy subjects or patients diagnosed with bronchiectasis, chronic obstructive pulmonary diseases (COPD), or interstitial lung disease (ILD). Differentiation capacity, a key property of the stem cells, was studied using a novel monolayer differentiation system. The differentiated cells were evaluated for alveolar and bronchial cell marker expression, and the quantified expression level of differentiated cells was further examined for their relationship with age and pulmonary function of the subjects. Results and Conclusions Differentiation of DASCs and tracheal stem cells (TSCs) yielded an alveolus-like structure and a tube-shaped structure, respectively, with distinct marker gene expression. Additionally, single-cell-derived clones showed diverse differentiation fates, even if the clones arise from identical or different individuals. More importantly, the alveolar differentiation potency was higher in DASCs derived from patients than from healthy people. The differentiation efficiency of DASCs also correlates with age in patients with bronchiectasis and ILD.