Yuan Hui, Li Yuwen, Kong Zihao, Peng Linya, Song Jiali, Hou Xiaoxue, Zhang Wen, Liu Rui, Feng Tiantong, Zhu Chuanlong
Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Stem Cells Int. 2024 Oct 23;2024:1273099. doi: 10.1155/2024/1273099. eCollection 2024.
Mesenchymal stem cells (MSCs) are highly effective in the treatment of acute liver failure (ALF). The efficacy of MSCs is closely related to the inflammatory environment. Therefore, we investigated the functional changes of MSCs in response to interleukin-33 (IL-33) stimulation. The results showed that bone marrow mesenchymal stem cells (BMSCs) pretreated with IL-33 had increased CCR2 expression, targeted CCL2 in the injured liver tissue, and improved the migration ability. Under LPS stimulation, the NF-B pathway of BMDM was activated, and its phenotype polarized to the M1-type, while BMSCs pretreated with IL-33 inhibited the NF-B pathway and enhanced M2 macrophage polarization. The M2-type macrophages could further inhibit hepatocytes inflammation, reduce hepatocytes apoptosis, and promote hepatocytes repair. These results suggest that IL-33 can enhance the efficacy of BMSCs in ALF and provide a new strategy for cell therapy of liver diseases.
间充质干细胞（MSCs）在急性肝衰竭（ALF）的治疗中具有高效性。MSCs的疗效与炎症环境密切相关。因此，我们研究了间充质干细胞在白细胞介素-33（IL-33）刺激下的功能变化。结果显示，用IL-33预处理的骨髓间充质干细胞（BMSCs）CCR2表达增加，靶向损伤肝组织中的CCL2，并提高了迁移能力。在脂多糖（LPS）刺激下，骨髓来源的巨噬细胞（BMDM）的NF-κB通路被激活，其表型极化为M1型，而用IL-33预处理的BMSCs抑制了NF-κB通路并增强了M2巨噬细胞极化。M2型巨噬细胞可进一步抑制肝细胞炎症，减少肝细胞凋亡，并促进肝细胞修复。这些结果表明，IL-33可增强BMSCs在ALF中的疗效，并为肝病的细胞治疗提供了一种新策略。
