1,738 results match your criteria intestinal organoids

TNF-α synergises with IFN-γ to induce caspase-8-JAK1/2-STAT1-dependent death of intestinal epithelial cells.

Cell Death Dis 2021 Sep 23;12(10):864. Epub 2021 Sep 23.

APC Microbiome Ireland, University College Cork, Cork, Ireland.

Rewiring of host cytokine networks is a key feature of inflammatory bowel diseases (IBD) such as Crohn's disease (CD). Th1-type cytokines-IFN-γ and TNF-α-occupy critical nodes within these networks and both are associated with disruption of gut epithelial barrier function. This may be due to their ability to synergistically trigger the death of intestinal epithelial cells (IECs) via largely unknown mechanisms. Read More

View Article and Full-Text PDF
September 2021

A Synthetic Hydrogel, VitroGel ORGANOID-3, Improves Immune Cell-Epithelial Interactions in a Tissue Chip Co-Culture Model of Human Gastric Organoids and Dendritic Cells.

Front Pharmacol 2021 6;12:707891. Epub 2021 Sep 6.

Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT, United States.

Immunosurveillance of the gastrointestinal epithelium by mononuclear phagocytes (MNPs) is essential for maintaining gut health. However, studying the complex interplay between the human gastrointestinal epithelium and MNPs such as dendritic cells (DCs) is difficult, since traditional cell culture systems lack complexity, and animal models may not adequately represent human tissues. Microphysiological systems, or tissue chips, are an attractive alternative for these investigations, because they model functional features of specific tissues or organs using microscale culture platforms that recreate physiological tissue microenvironments. Read More

View Article and Full-Text PDF
September 2021

ATCC 6475 metabolites upregulate the serotonin transporter in the intestinal epithelium.

Benef Microbes 2021 Sep 22:1-18. Epub 2021 Sep 22.

Department of Pathology & Immunology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA.

The serotonin transporter (SERT) readily takes up serotonin (5-HT), thereby regulating the availability of 5-HT within the intestine. In the absence of SERT, 5-HT remains in the interstitial space and has the potential to aberrantly activate the many 5-HT receptors distributed on the epithelium, immune cells and enteric neurons. Perturbation of SERT is common in many gastrointestinal disorders as well as mouse models of colitis. Read More

View Article and Full-Text PDF
September 2021

Single-cell DNA and RNA sequencing reveals the dynamics of intra-tumor heterogeneity in a colorectal cancer model.

BMC Biol 2021 Sep 21;19(1):207. Epub 2021 Sep 21.

Division of Bioinformatics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background: Intra-tumor heterogeneity (ITH) encompasses cellular differences in tumors and is related to clinical outcomes such as drug resistance. However, little is known about the dynamics of ITH, owing to the lack of time-series analysis at the single-cell level. Mouse models that recapitulate cancer development are useful for controlled serial time sampling. Read More

View Article and Full-Text PDF
September 2021

Transplantion of predominant Lactobacilli from native hens to commercial hens could indirectly regulate their ISC activity by improving intestinal microbiota.

Microb Biotechnol 2021 Sep 18. Epub 2021 Sep 18.

Department of Veterinary Medicine, Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou, 310058, China.

In poultry, HyLine (HL) Hens are known for their excellent laying performance. However, ZhenNing (ZN) Hens, a native chicken breed in China, are known for their unique flavour. The intestinal mucosa, which is the main organ for nutrient absorption, could affect livestock product quality. Read More

View Article and Full-Text PDF
September 2021

A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses.

Nat Commun 2021 09 17;12(1):5498. Epub 2021 Sep 17.

Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, Netherlands.

Rapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, leading to discoveries that may not be translated to the clinic. Intestinal organoids are increasingly used to model human disease and are amenable to genetic engineering. Read More

View Article and Full-Text PDF
September 2021

The circadian clock gene, Bmal1, regulates intestinal stem cell signaling and represses tumor initiation.

Cell Mol Gastroenterol Hepatol 2021 Sep 14. Epub 2021 Sep 14.

Department of Biomedical Sciences, University of Windsor, Windsor, N9B 3P4, Ontario. Electronic address:

Background: Circadian rhythms are daily physiological oscillations driven by the circadian clock: a 24-hour transcriptional timekeeper that regulates hormones, inflammation, and metabolism. Circadian rhythms are known to be important for health, but whether their loss contributes to colorectal cancer is not known.

Aims: We tested the non-redundant clock gene, Bmal1, in intestinal homeostasis and tumorigenesis, using the Apc model of colorectal cancer. Read More

View Article and Full-Text PDF
September 2021

Human Adipose Mesenchymal Stem Cell-derived Exosomes Protect Mice from DSS-Induced Inflammatory Bowel Disease by Promoting Intestinal-stem-cell and Epithelial Regeneration.

Aging Dis 2021 Sep 1;12(6):1423-1437. Epub 2021 Sep 1.

1Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.

Inflammatory bowel disease (IBD) remains a severe disease for most patients, with its incidence and prevalence increasingly globally. Currently, there is no effective treatments for IBD, and traditional treatments have multiple side effects. Therefore, novel therapeutic strategies or alternative drugs are urgently needed. Read More

View Article and Full-Text PDF
September 2021

Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs).

Genes Dis 2021 Nov 28;8(6):814-826. Epub 2021 Jan 28.

Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 606037, USA.

Intestinal cancers are developed from intestinal epithelial stem cells (ISCs) in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor genes. ISCs play a key role in maintaining the homeostasis of gut epithelium. In 2009, Sato et al established a three-dimensional culture system, which mimicked the niche microenvironment by employing the niche factors, and successfully grew crypt ISCs into organoids or Mini-guts . Read More

View Article and Full-Text PDF
November 2021

STRAP is a Critical Mediator of APC Mutation-Induced Intestinal Tumorigenesis through a Feed-Forward Mechanism.

Gastroenterology 2021 Sep 11. Epub 2021 Sep 11.

Division of Hematology and Oncology, Department of Medicine, UAB Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Birmingham Veterans Affairs Medical Center, Birmingham, AL 35233, USA. Electronic address:

Background And Aims: Inactivation of the Apc gene is a critical early event in the development of sporadic colorectal cancer (CRC). The expression of serine-threonine kinase receptor-associated protein (STRAP) is elevated in CRCs and is associated with poor outcomes. We investigated the role of STRAP in Apc mutation-induced intestinal tumor initiation and progression. Read More

View Article and Full-Text PDF
September 2021

Low-viscosity matrix suspension culture enables scalable analysis of patient-derived organoids and tumoroids from the large intestine.

Commun Biol 2021 09 13;4(1):1067. Epub 2021 Sep 13.

Personalised Oncology Division, The Walter and Eliza Hall Institute of Medial Research, Parkville, Victoria, 3052, Australia.

Cell embedment into a solid support matrix is considered essential for the culture of intestinal epithelial organoids and tumoroids, but this technique presents challenges that impede scalable culture expansion, experimental manipulation, high-throughput screening and diagnostic applications. We have developed a low-viscosity matrix (LVM) suspension culture method that enables efficient establishment and propagation of organoids and tumoroids from the human large intestine. Organoids and tumoroids cultured in LVM suspension recapitulate the morphological development observed in solid matrices, with tumoroids reflecting the histological features and genetic heterogeneity of primary colorectal cancers. Read More

View Article and Full-Text PDF
September 2021

Monolayer platform using human biopsy-derived duodenal organoids for pharmaceutical research.

Mol Ther Methods Clin Dev 2021 Sep 19;22:263-278. Epub 2021 May 19.

Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.

The human small intestine is the key organ for absorption, metabolism, and excretion of orally administered drugs. To preclinically predict these reactions in drug discovery research, a cell model that can precisely recapitulate the human intestinal monolayer is desired. In this study, we developed a monolayer platform using human biopsy-derived duodenal organoids for application to pharmacokinetic studies. Read More

View Article and Full-Text PDF
September 2021

Organoids and Their Use in Modeling Gut Epithelial Cell Lineage Differentiation and Barrier Properties During Intestinal Diseases.

Front Cell Dev Biol 2021 13;9:732137. Epub 2021 Aug 13.

Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, QC, Canada.

Maintenance of intestinal epithelium homeostasis is a complex process because of the multicellular and molecular composition of the gastrointestinal wall and the involvement of surrounding interactive signals. The complex nature of this intestinal barrier system poses challenges in the detailed mechanistic understanding of intestinal morphogenesis and the onset of several gut pathologies, including intestinal inflammatory disorders, food allergies, and cancer. For several years, the gut scientific community has explored different alternatives in research involving animals and models consisting of cultured monolayers derived from the immortalized or cancerous origin cell lines. Read More

View Article and Full-Text PDF

Gutsy science: In vitro systems of the human intestine to model oral drug disposition.

Pharmacol Ther 2021 Aug 31:107962. Epub 2021 Aug 31.

Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA 98195, USA. Electronic address:

The intestine has important gate-keeping functions that can profoundly affect the systemic blood exposure of orally administered drugs. Thus, characterizing a new molecular entity's (NME) disposition within the intestine is of utmost importance in drug development. While currently used in vitro systems, such as Ussing chamber, precision-cut intestinal slices, immortalized cell lines, and primary enterocytes provide substantial knowledge about drug absorption and the intestinal first-pass effect, they remain sub-optimal for quantitatively predicting this process and the oral bioavailability of many drugs. Read More

View Article and Full-Text PDF

Inflation comes before the fall: How epithelial stretch drives crypt fission.

Cell Stem Cell 2021 09;28(9):1505-1506

Centre for Craniofacial and Regenerative Biology, King's College London, London SE1 9RT, UK. Electronic address:

In this issue of Cell Stem Cell, Tallapragada et al. (2021) present an intestinal organoid culture system for high-throughput live imaging to investigate niche-independent mechanisms of crypt fission. They find that Piezo activity downregulates Lgr5 expression in stretched epithelial cells within inflated organoids, which form multiple new crypts upon collapse. Read More

View Article and Full-Text PDF
September 2021

3D Organoid Culture From Adult Salivary Gland Tissues as an Modeling of Salivary Gland Morphogenesis.

Front Cell Dev Biol 2021 12;9:698292. Epub 2021 Aug 12.

Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea.

Lumen formation of salivary glands has been investigated using or rudiment culture models. In this study, we used a three-dimensional (3D) salivary gland organoid culture system and demonstrated that lumen formation could be recapitulated in mouse SMG organoids. In our organoid culture system, lumen formation was induced by vasoactive intestinal peptide and accelerated by treatment with RA. Read More

View Article and Full-Text PDF

Organ-on-chip approaches for intestinal 3D in vitro modelling.

Cell Mol Gastroenterol Hepatol 2021 Aug 25. Epub 2021 Aug 25.

i3S - Institute for Research and Innovation in Health (Instituto de Investigação e Inovação em Saúde), University of Porto, 4200-135 Porto, Portugal; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal. Electronic address:

The intestinal epithelium has one of the highest turnover rates in the human body, which is supported by intestinal stem cells. Culture models of intestinal physiology have been evolving to incorporate different tissue and microenvironmental elements. However, these models also display gaps that limit their similarity with native conditions. Read More

View Article and Full-Text PDF

Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids.

Pharmaceutics 2021 Aug 17;13(8). Epub 2021 Aug 17.

Chair of Nutrition and Immunology, Technische Universität München, 85354 Freising, Germany.

The intestinal epithelium critically contributes to oral bioavailability of drugs by constituting an important site for drug absorption and metabolism. In particular, intestinal epithelial cells (IEC) actively serve as gatekeepers of drug and nutrient availability. IECs' transport processes and metabolism are interrelated to the whole-body metabolic state and represent potential points of origin as well as therapeutic targets for a variety of diseases. Read More

View Article and Full-Text PDF

Assessing donor-to-donor variability in human intestinal organoid cultures.

Stem Cell Reports 2021 Sep 26;16(9):2364-2378. Epub 2021 Aug 26.

Exploratory Science Center, Merck & Co., Inc., Cambridge, MA 02141, USA. Electronic address:

Donor-to-donor variability in primary human organoid cultures has not been well characterized. As these cultures contain multiple cell types, there is greater concern that variability could lead to increased noise. In this work we investigated donor-to-donor variability in human gut adult stem cell (ASC) organoids. Read More

View Article and Full-Text PDF
September 2021

Role of Ras in regulation of intestinal epithelial cell homeostasis and crosstalk with Wnt signaling.

PLoS One 2021 26;16(8):e0256774. Epub 2021 Aug 26.

Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan.

Cross talk between different signaling pathways is thought to be important for regulation of homeostasis of, as well as oncogenesis of, the intestinal epithelium. Expression of an active form of K-Ras specifically in intestinal epithelial cells (IECs) of mice (IEC-RasDA mice) resulted in the development of hyperplasia in the small intestine and colon of mice. IEC-RasDA mice also manifested the increased proliferation of IECs. Read More

View Article and Full-Text PDF

Melatonin reduces inflammation in intestinal cells, organoids and intestinal explants.

Inflammopharmacology 2021 Aug 24. Epub 2021 Aug 24.

Anorectal Surgery, Tangshan Gongren Hospital, Tangshan, 063000, Hebei, China.

Inflammatory bowel diseases (IBDs) are chronic and recurrent diseases that often occur in young people and place a heavy burden on public health in both developed and developing countries. Melatonin has been confirmed to be useful in various diseases, including Alzheimer's disease, liver injuries and diseases, and cancers, while its role in IBDs remains unclear. To uncover the function of melatonin in IBDs, three intestinal models, including Caco-2 cells, 3D intestinal organoids and intestinal explants, were used. Read More

View Article and Full-Text PDF

Intestinal organoid-based 2D monolayers mimic physiological and pathophysiological properties of the pig intestine.

PLoS One 2021 23;16(8):e0256143. Epub 2021 Aug 23.

Institute for Physiology and Cell Biology, University of Veterinary Medicine Hannover, Hannover, Germany.

Gastrointestinal infectious diseases remain an important issue for human and animal health. Investigations on gastrointestinal infectious diseases are classically performed in laboratory animals leading to the problem that species-specific models are scarcely available, especially when it comes to farm animals. The 3R principles of Russel and Burch were achieved using intestinal organoids of porcine jejunum. Read More

View Article and Full-Text PDF

Invasive Pathobionts Contribute to Colon Cancer Initiation by Counterbalancing Epithelial Antimicrobial Responses.

Cell Mol Gastroenterol Hepatol 2021 Aug 18. Epub 2021 Aug 18.

Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan, Republic of China. Electronic address:

Background & Aims: Microbiota dysbiosis and mucosa-associated bacteria are involved in colorectal cancer progression. We hypothesize that an interaction between virulent pathobionts and epithelial defense promotes tumorigenesis.

Methods And Results: Our study showed that antibiotic treatment at midphase but not early or late phase reduced mouse tumor burden, suggesting a time-specific host-microbe interplay. Read More

View Article and Full-Text PDF

Current Trends and Research Topics Regarding Intestinal Organoids: An Overview Based on Bibliometrics.

Front Cell Dev Biol 2021 3;9:609452. Epub 2021 Aug 3.

Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.

Currently, research on intestinal diseases is mainly based on animal models and cell lines in monolayers. However, these models have drawbacks that limit scientific advances in this field. Three-dimensional (3D) culture systems named organoids are emerging as a reliable research tool for recapitulating the human intestinal epithelium and represent a unique platform for patient-specific drug testing. Read More

View Article and Full-Text PDF

Therapeutic targeting of endoplasmic reticulum stress in acute graft-versus-host disease.

Haematologica 2021 Aug 19. Epub 2021 Aug 19.

Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany; German Cancer Consortium (DKTK), Partner site Freiburg; and German Cancer Research Center (DKFZ), Heidelberg.

Acute graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), a potentially curative treatment for leukemia. Endoplasmic reticulum (ER) stress occurs when the protein folding capacity of the ER is oversaturated. How ER stress modulates tissue homeostasis in the context of alloimmunity is not well understood. Read More

View Article and Full-Text PDF

Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon.

Mol Nutr Food Res 2021 Aug 18:e2100539. Epub 2021 Aug 18.

Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, 77843, USA.

Scope: This study investigates the mechanism of action and functional effects of coffee extracts in colonic cells, on intestinal stem cell growth, and inhibition of dextran sodium sulfate (DSS)-induced intestinal barrier damage in mice.

Methods And Results: Aqueous coffee extracts induced Ah receptor (AhR) -responsive CYP1A1, CYP1B1, and UGT1A1 gene expression in colon-derived Caco2 and YAMC cells. Tissue-specific AhR knockout (AhR x Lgr5-GFP-CreERT2 x Villin-Cre), wild-type (Lgr5-CreERT2 x Villin-Cre) mice are sources of stem cell enriched organoids and both coffee extracts and norharman, an AhR-active component of these extracts inhibited stem cell growth. Read More

View Article and Full-Text PDF

Characterization of an in vitro 3D intestinal organoid model by using massive RNAseq-based transcriptome profiling.

Sci Rep 2021 Aug 17;11(1):16668. Epub 2021 Aug 17.

Leibniz Institute on Aging, Fritz Lipmann Institute (FLI), Jena, Germany.

Organoids culture provides unique opportunities to study human diseases and to complement animal models. Several organs and tissues can be in vitro cultured in 3D structures resembling in vivo tissue organization. Organoids culture contains most of the cell types of the original tissue and are maintained by growth factors mimicking the in vivo state. Read More

View Article and Full-Text PDF

Live cell tagging tracking and isolation for spatial transcriptomics using photoactivatable cell dyes.

Nat Commun 2021 08 17;12(1):4995. Epub 2021 Aug 17.

Institute for Medical Engineering & Science, MIT, Cambridge, MA, USA.

A cell's phenotype and function are influenced by dynamic interactions with its microenvironment. To examine cellular spatiotemporal activity, we developed SPACECAT-Spatially PhotoActivatable Color Encoded Cell Address Tags-to annotate, track, and isolate cells while preserving viability. In SPACECAT, samples are stained with photocaged fluorescent molecules, and cells are labeled by uncaging those molecules with user-patterned near-UV light. Read More

View Article and Full-Text PDF

Translation initiation factor eIF2Bε promotes Wnt-mediated clonogenicity and global translation in intestinal epithelial cells.

Stem Cell Res 2021 Aug 11;55:102499. Epub 2021 Aug 11.

Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Tytgat Institute for Liver and Intestinal Research, Meibergdreef 71, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Internal Medicine, Meibergdreef 9, Amsterdam, the Netherlands. Electronic address:

Modulation of global mRNA translation, which is essential for intestinal stem cell function, is controlled by Wnt signaling. Loss of tumor supressor APC in stem cells drives adenoma formation through hyperactivion of Wnt signaling and dysregulated translational control. It is unclear whether factors that coordinate global translation in the intestinal epithelium are needed for APC-driven malignant transformation. Read More

View Article and Full-Text PDF

Generation and Characterization of Murine Oral Mucosal Organoid Cultures.

J Vis Exp 2021 Jul 31(173). Epub 2021 Jul 31.

Mildred Scheel Early Career Centre (MSNZ) for Cancer Research, IZKF/MSNZ, University Hospital Würzburg;

The mucous lining covering the inside of our mouth, the oral mucosa, is a highly compartmentalized tissue and can be subdivided into the buccal mucosa, gingiva, lips, palate, and tongue. Its uppermost layer, the oral epithelium, is maintained by adult stem cells throughout life. Proliferation and differentiation of adult epithelial stem cells have been intensively studied using in vivo mouse models as well as two-dimensional (2D) feeder-cell based in vitro models. Read More

View Article and Full-Text PDF