biostudies-literatureMeng FOpen Research Fund of Shandong Key Laboratory of Biophysics of Dezhou CollegeNatural Science Foundation of Beijing MunicipalityNational Key Research and Development Program of China Stem Cell and Translational ResearchShanghai Pilot Program for Basic Research - Fudan University 21TQ1400100Natural Science Foundation of Shandong ProvinceNational Natural Science Foundation of China39https://www.ebi.ac.uk/biostudies/studies/S-EPMC9626719biostudies-literatureUnknown11(1)Intestinal organoids, derived from intestinal stem cell self-organization, recapitulate the tissue structures and behaviors of the intestinal epithelium, which hold great potential for the study of developmental biology, disease modeling, and regenerative medicine. The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development. However, the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors. Here, we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells. Furthermore, mechanical stretching stimulates the expansion of SOX9⁺ progenitors by activating the Wnt/β-Catenin signaling. These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells, thus benefiting organoid growth. Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors, paving the way for the application of mechanical forces in organoid-based models.Cell regeneration (London, England)Mechanical stretching boosts expansion and regeneration of intestinal organoids through fueling stem cell self-renewal.PMC9626719Z200017119720016207108511972002SD2018BP0052018YFA010940032022022ZR2019PC02621TQ003Yang LHuang JZhao BCui WShen CWang JMeng FCao ZZhou BXu SXiong CNi CWang XLin KfalseMechanical stretching boosts expansion and regeneration of intestinal organoids through fueling stem cell self-renewal.Intestinal organoids, derived from intestinal stem cell self-organization, recapitulate the tissue structures and behaviors of the intestinal epithelium, which hold great potential for the study of developmental biology, disease modeling, and regenerative medicine. The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development. However, the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors. Here, we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells. Furthermore, mechanical stretching stimulates the expansion of SOX9⁺ progenitors by activating the Wnt/β-Catenin signaling. These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells, thus benefiting organoid growth. Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors, paving the way for the application of mechanical forces in organoid-based models.2022-01-01T00:00:00Z2022 Nov2024-10-18T22:05:39.887Z2024-10-18T22:05:39.887ZS-EPMC96267193631979910.1186/s13619-022-00137-4