The long-term influence of low X-ray irradiation increases lipid peroxidation (LP) in radiosensitive (bone marrow, enterocytes of small intenstine) and in relatively radioresistant blood cells (erythrocytes). The activation of antioxidant system enzymes in observed cells does not decrease LP intensity. We concluded that additional administration of alpha-tocopherol provided the decrease of the first and end products of LP in the observed tissues mostly in the beginning of the experiment. Antioxidant effect of the preparation is more significant in cells with high proliferative activity but normal activity of enzymes was not determined.
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Integration of Stromal Cells and Hydrogel Below Epithelium Results in Optimal Barrier Properties of Small Intestine Organoid Models.
Biomedicines
December 2024
Department of Molecular Cell Biology and Immunology, Amsterdam UMC Location Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
: The barrier properties of the human small intestine play a crucial role in regulating digestion, nutrient absorption and drug metabolism. Current in vitro organotypic models consist only of an epithelium, which does not take into account the possible role of stromal cells such as fibroblasts or the extracellular matrix (ECM) which could contribute to epithelial barrier properties. Therefore, the aim of this study was to determine whether these stromal cells or ECM were beneficial or detrimental to barrier function when incorporated into an organotypic human small intestine model.
View Article and Find Full Text PDFUnraveling Caco-2 Cells through Functional and Transcriptomic Assessments.
Regul Toxicol Pharmacol
January 2025
Division of Applied Regulatory Science, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, The U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, United States of America. Electronic address:
The static Caco-2 monolayer is an extensively utilized model for predicting the permeability of small molecules during the drug development process. While these cells can differentiate and develop key functional and morphological features that emulate human enterocytes, they do not fully replicate the complexity of human intestinal physiology. In this study, we investigated functional and morphological aspects of Caco-2 cells, alongside their transcriptomic profiles, with a particular emphasis on genes encoding drug-metabolizing enzymes and drug transporters.
View Article and Find Full Text PDFA tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation.
Nat Commun
January 2025
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
A balance between stem cell self-renewal and differentiation is required to maintain concurrent proliferation and cellular diversification in organoids; however, this has proven difficult in homogeneous cultures devoid of in vivo spatial niche gradients for adult stem cell-derived organoids. In this study, we leverage a combination of small molecule pathway modulators to enhance the stemness of organoid stem cells, thereby amplifying their differentiation potential and subsequently increasing cellular diversity within human intestinal organoids without the need for artificial spatial or temporal signaling gradients. Moreover, we demonstrate that this balance between self-renewal and differentiation can be effectively and reversibly shifted from secretory cell differentiation to the enterocyte lineage with enhanced proliferation using BET inhibitors, or unidirectional differentiation towards specific intestinal cell types by manipulating in vivo niche signals such as Wnt, Notch, and BMP.
View Article and Find Full Text PDFMesenchymal cell contractility regulates villus morphogenesis and intestinal architecture.
Dev Biol
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Department of Dermatology, Duke University Medical Center, Durham, NC, 27710, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC, 27710, USA. Electronic address:
Article Synopsis
- The small intestine's absorptive surface area is increased by structures called villi, which are influenced by stromal cells promoting bending through actomyosin contraction.
- Researchers induced contractility in intestinal mesenchyme, leading to villi that were shorter and wider than normal due to architectural defects, despite increased cell proliferation.
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MUC17 is an essential small intestinal glycocalyx component that is disrupted in Crohn's disease.
JCI Insight
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Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
Crohn's disease (CD) is the chronic inflammation of the terminal ileum and colon triggered by a dysregulated immune response to bacteria, but insights into specific molecular perturbations at the critical bacteria-epithelium interface are limited. Here we report that the membrane mucin MUC17 protected small intestinal enterocytes against commensal and pathogenic bacteria. In non-inflamed CD ileum, reduced MUC17 levels and a compromised glycocalyx barrier allowed recurrent bacterial contact with enterocytes.
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