Du Sheng, Jin Jing, Tang Chunli, Su Zhuquan, Wang Lulin, Chen Xinyuan, Zhang Mengni, Zhu Yiping, Wang Jiaojiao, Ju Chunrong, Song Xinyu, Li Shiyue
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangzhou National Laboratory, Guangzhou, China.
Cell Prolif. 2025 Jun;58(6):e13812. doi: 10.1111/cpr.13812. Epub 2025 Jan 26.
SARS-CoV-2 infection and the resultant COVID-19 pneumonia cause significant damage to the airway and lung epithelium. This damage manifests as mucus hypersecretion, pulmonary inflammation and fibrosis, which often lead to long-term complications collectively referred to as long COVID or post-acute sequelae of COVID-19 (PASC). The airway epithelium, as the first line of defence against respiratory pathogens, depends on airway basal stem cells (BSCs) for regeneration. Alterations in BSCs are associated with impaired epithelial repair and may contribute to the respiratory complications observed in PASC. Given the critical role of BSCs in maintaining epithelial integrity, understanding their alterations in COVID-19 is essential for developing effective therapeutic strategies. This study investigates the intrinsic properties of BSCs derived from COVID-19 patients and evaluates the modulatory effects of mesenchymal stem cells (MSCs). Through a combination of functional assessments and transcriptomic profiling, we identified key phenotypic and molecular deviations in COVID-19 patient-derived BSCs, including goblet cell hyperplasia, inflammation and fibrosis, which may underlie their contribution to PASC. Notably, MSC co-culture significantly mitigated these adverse effects, potentially through modulation of the interferon signalling pathway. This is the first study to isolate BSCs from COVID-19 patients in the Chinese population and establish a COVID-19 BSC-based xenograft model. Our findings reveal critical insights into the role of BSCs in epithelial repair and their inflammatory alterations in COVID-19 pathology, with potential relevance to PASC and virus-induced respiratory sequelae. Additionally, our study highlights MSC-based therapies as a promising strategy to address respiratory sequelae and persistent symptoms.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染及由此导致的冠状病毒病2019（COVID-19）肺炎会对气道和肺上皮造成严重损害。这种损害表现为黏液分泌过多、肺部炎症和纤维化，常导致统称为“长新冠”或COVID-19急性后遗症（PASC）的长期并发症。气道上皮作为抵御呼吸道病原体的第一道防线，依靠气道基底干细胞（BSCs）进行再生。BSCs的改变与上皮修复受损有关，可能导致PASC中观察到的呼吸并发症。鉴于BSCs在维持上皮完整性方面的关键作用，了解其在COVID-19中的改变对于制定有效的治疗策略至关重要。本研究调查了COVID-19患者来源的BSCs的内在特性，并评估了间充质干细胞（MSCs）的调节作用。通过功能评估和转录组分析相结合的方法，我们确定了COVID-19患者来源的BSCs的关键表型和分子偏差，包括杯状细胞增生、炎症和纤维化，这可能是它们对PASC产生影响的基础。值得注意的是，MSC共培养显著减轻了这些不良反应，可能是通过调节干扰素信号通路实现的。这是首次在中国人群中从COVID-19患者中分离出BSCs并建立基于COVID-19 BSC的异种移植模型的研究。我们的研究结果揭示了BSCs在上皮修复中的作用及其在COVID-19病理学中的炎症改变的关键见解，与PASC和病毒诱导的呼吸后遗症可能相关。此外，我们的研究强调基于MSC的疗法是解决呼吸后遗症和持续症状的一种有前景的策略。
