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  3. Human placenta mesenchymal stromal cells alleviate intestinal inflammation and repair intestinal barrier function by activating AMPK-FXR pathway

Human placenta mesenchymal stromal cells alleviate intestinal inflammation and repair intestinal barrier function by activating AMPK-FXR pathway

  • Commun Biol. 2025 May 30;8(1):830. doi: 10.1038/s42003-025-08261-y.
Ruo Wang # 1,  Bing Feng # 1,  Qigu Yao 1,  Qiaoling Pan 1,  Jiong Yu 1 2 3,  Chaoxu Liu 4,  Jinhai Wang 4,  Lanjuan Li 1 2,  Hongcui Cao 5 6,  Jue Xie 7 8 9
Affiliations

Affiliations

  • 1 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.
  • 2 Jinan Microecological Biomedicine Shandong Laboratory, Jinan City, China.
  • 3 Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, China.
  • 4 Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, China.
  • 5 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. hccao@zju.edu.cn.
  • 6 Zhejiang Key Laboratory for Diagnosis and Treatment of Physic-chemical and Aging-related Injuries, 79 Qingchun Rd, Hangzhou City, China. hccao@zju.edu.cn.
  • 7 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. zyyyxj2011@zju.edu.cn.
  • 8 Department of Blood Transfusion, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd, Hangzhou City, China. zyyyxj2011@zju.edu.cn.
  • 9 Zhejiang Key Laboratory for Diagnosis and Treatment of Physic-chemical and Aging-related Injuries, 79 Qingchun Rd, Hangzhou City, China. zyyyxj2011@zju.edu.cn.
  • # Contributed equally.
PMID: 40447793 DOI: 10.1038/s42003-025-08261-y
Abstract

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.

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