Zhou Yuchuan, Xiao Jianbo, Peng Shu, Pang Xiao, Ma Daiyuan, Gui Yan, Zhang Hongpan, Li Zhike
1Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China.
Department of Neurology, Nanchong Central Hospital, Nanchong, Sichuan, China.
Stem Cell Rev Rep. 2025 Oct;21(7):2298-2309. doi: 10.1007/s12015-025-10938-0. Epub 2025 Jul 29.
Mesenchymal stem cells (MSCs) are frequently employed in transplantation therapies for chronic inflammatory diseases. However, the impact of the inflammatory microenvironment on the functionality of MSCs remains poorly understood. Tumor necrosis factor-alpha (TNF-α) is a prevalent inflammatory mediator at transplantation sites, and prior research has indicated that the role of TNF-α in MSCs transplantation is ambiguous. The mechanisms by which TNF-α modulates the function of MSCs require further elucidation. To investigate this, we conducted comprehensive OLINK proteomic and transcriptomic analyses. The results showed After TNF stimulation, MSCs underwent apoptosis and aging, and their immune regulation, cell migration, and differentiation function were reduced. The signaling pathways involved include NF-KB, MAPK, stem cell pluripotency, etc. In conclusion, TNF activates the immune response of MSCs and impairs their stemness, thereby significantly affecting their capacity for cartilage differentiation.
间充质干细胞(MSCs)常用于慢性炎症性疾病的移植治疗。然而,炎症微环境对MSCs功能的影响仍知之甚少。肿瘤坏死因子-α(TNF-α)是移植部位普遍存在的炎症介质,先前的研究表明TNF-α在MSCs移植中的作用尚不明确。TNF-α调节MSCs功能的机制需要进一步阐明。为了对此进行研究,我们进行了全面的OLINK蛋白质组学和转录组学分析。结果显示,TNF刺激后,MSCs发生凋亡和衰老,其免疫调节、细胞迁移和分化功能降低。涉及的信号通路包括NF-KB、MAPK、干细胞多能性等。总之,TNF激活MSCs的免疫反应并损害其干性,从而显著影响其软骨分化能力。