Wang Ruo, Feng Bing, Yao Qigu, Pan Qiaoling, Yu Jiong, Liu Chaoxu, Wang Jinhai, Li Lanjuan, Cao Hongcui, Xie Jue
State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, China.
Jinan Microecological Biomedicine Shandong Laboratory, Jinan City, China.
Commun Biol. 2025 May 30;8(1):830. doi: 10.1038/s42003-025-08261-y.
Crohn's disease (CD) has a complex pathogenesis; there is currently no effective treatment. Mesenchymal stromal cells (MSCs) are a potential therapeutic option for CD. It is important to systematically evaluate the safety and effectiveness of MSCs and their mechanism for the treatment of CD to support their clinical application. Here, the safety and effectiveness of MSCs from the human placenta (hPMSCs) are evaluated. All the indicators show that hPMSC transplantation is safe and effectively alleviates intestinal inflammation, reduces intestinal apoptosis and fibrosis, and promotes recovery of the intestinal barrier in mice and organoids. IGFBP-4 is the most expressed by hPMSCs and is verified to play a therapeutic role by activating the AMPK-FXR pathway to alleviate intestinal inflammation and repair the intestinal barrier function. Our findings demonstrate that hPMSCs alleviate CD by activating the AMPK-FXR pathway with IGFBP-4 to reduce intestinal inflammation and repair intestinal barrier function.
克罗恩病（CD）发病机制复杂，目前尚无有效治疗方法。间充质基质细胞（MSCs）是治疗CD的一种潜在选择。系统评估MSCs治疗CD的安全性、有效性及其作用机制对支持其临床应用具有重要意义。在此，对人胎盘间充质基质细胞（hPMSCs）的安全性和有效性进行评估。所有指标均表明，hPMSC移植是安全的，可有效减轻小鼠和类器官的肠道炎症，减少肠道细胞凋亡和纤维化，并促进肠道屏障恢复。IGFBP-4在hPMSCs中表达最为丰富，经证实可通过激活AMPK-FXR通路发挥治疗作用，减轻肠道炎症并修复肠道屏障功能。我们的研究结果表明，hPMSCs通过激活AMPK-FXR通路及IGFBP-4减轻CD，以减少肠道炎症并修复肠道屏障功能。
