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

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.