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https://www.readbyqxmd.com/read/28646678/bioengineering-for-intestinal-organoid-cultures
#1
REVIEW
Ge-Ah Kim, Jason R Spence, Shuichi Takayama
Recent advances allow access to human cell-based intestinal organoids that recreate human physiology to levels not possible with conventional 2D cell cultures. Despite their huge potential, there are many challenges that remain. This review will cover recent bioengineering approaches to improve organoid maturation, scale up, reproducibility and analysis. The first section covers the advances in engineering the culture environment, followed by the section on tools for micro-manipulation and analysis of organoids...
June 21, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28643936/phenotypic-analysis-of-organoids-by-proteomics
#2
REVIEW
Alexis Gonneaud, Claude Asselin, François Boudreau, François-Michel Boisvert
The development of 3D cell cultures into self-organizing organ-like structures named organoids provides a model that better reflects in vivo organ physiology and their functional properties. Organoids have been established from several organs, such as the intestine, prostate, brain, liver, kidney and pancreas. With recent advances in high-throughput and -omics profiling technologies, it is now possible to study the mechanisms of cellular organisation at the systems level. It is therefore not surprising that these methods are now used to characterize organoids at the transcriptomic, proteomic, chromatin state and transcription factor DNA-binding levels...
June 23, 2017: Proteomics
https://www.readbyqxmd.com/read/28628120/intestinal-cancer-progression-by-mutant-p53-through-the-acquisition-of-invasiveness-associated-with-complex-glandular-formation
#3
M Nakayama, E Sakai, K Echizen, Y Yamada, H Oshima, T-S Han, R Ohki, S Fujii, A Ochiai, S Robine, D C Voon, T Tanaka, M M Taketo, M Oshima
Tumor suppressor TP53 is frequently mutated in colorectal cancer (CRC), and most mutations are missense type. Although gain-of-functions by mutant p53 have been demonstrated experimentally, the precise mechanism for malignant progression in in vivo tumors remains unsolved. We generated Apc(Δ716) Trp53(LSL•R270H) villin-CreER compound mice, in which mutant p53(R270H) was expressed in the intestinal epithelia upon tamoxifen treatment, and examined the intestinal tumor phenotypes and tumor-derived organoids...
June 19, 2017: Oncogene
https://www.readbyqxmd.com/read/28628110/colonic-organoids-derived-from-human-induced-pluripotent-stem-cells-for-modeling-colorectal-cancer-and-drug-testing
#4
Miguel Crespo, Eduardo Vilar, Su-Yi Tsai, Kyle Chang, Sadaf Amin, Tara Srinivasan, Tuo Zhang, Nina H Pipalia, Huanhuan Joyce Chen, Mavee Witherspoon, Miriam Gordillo, Jenny Zhaoying Xiang, Frederick R Maxfield, Steven Lipkin, Todd Evans, Shuibing Chen
With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived COs represent colon rather than small intestine, containing stem cells, transit-amplifying cells, and the expected spectrum of differentiated cells, including goblet and endocrine cells. We applied this strategy to iPSCs derived from patients with familial adenomatous polyposis (FAP-iPSCs) harboring germline mutations in the WNT-signaling-pathway-regulator gene encoding APC, and we generated COs that exhibit enhanced WNT activity and increased epithelial cell proliferation, which we used as a platform for drug testing...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28614706/enhanced-rate-of-acquisition-of-point-mutations-in-mouse-intestinal-adenomas-compared-to-normal-tissue
#5
Natalia Lugli, Vasilis S Dionellis, Paloma Ordóñez-Morán, Irene Kamileri, Sotirios K Sotiriou, Joerg Huelsken, Thanos D Halazonetis
The most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T substitution in the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation of a normal cell into a precancerous/cancer cell. Here, we isolated single intestinal crypts derived from normal tissue or from adenomas of Apc(min/+) mice, expanded them minimally in vitro as organoids, and performed exome sequencing to identify point mutations that had been acquired in vivo at the single-cell level...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28614372/intestinal-organoids-model-human-responses-to-infection-by-commensal-and-shiga-toxin-producing-escherichia-coli
#6
Sayali S Karve, Suman Pradhan, Doyle V Ward, Alison A Weiss
Infection with Shiga toxin (Stx) producing Escherichia coli O157:H7 can cause the potentially fatal complication hemolytic uremic syndrome, and currently only supportive therapy is available. Lack of suitable animal models has hindered study of this disease. Induced human intestinal organoids (iHIOs), generated by in vitro differentiation of pluripotent stem cells, represent differentiated human intestinal tissue. We show that iHIOs with addition of human neutrophils can model E. coli intestinal infection and innate cellular responses...
2017: PloS One
https://www.readbyqxmd.com/read/28607910/exploiting-induced-senescence-in-intestinal-organoids-to-drive-enteroendocrine-cell-expansion
#7
EDITORIAL
Robert G Ramsay, Helen E Abud
No abstract text is available yet for this article.
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28600348/loss-of-the-wnt-receptor-frizzled7-in-the-gastric-epithelium-is-deleterious-and-triggers-rapid-repopulation-in-vivo
#8
Dustin J Flanagan, Nicholas Barker, Cameron Nowell, Hans Clevers, Matthias Ernst, Toby J Phesse, Elizabeth Vincan
The gastric epithelium consists of tubular glandular units each containing several differentiated cells types, and populations of stem cells, which enable the stomach to secrete the acid, mucus and various digestive enzymes required for its function. Cell signalling provides cues to regulate development and homeostasis of adult tissues, however very little is known about which cell signalling pathways are required for homeostasis of the gastric epithelium. Many diseases, such as cancer, arise as a result of deregulation to signalling pathways that regulate homeostasis of the diseased organ...
June 9, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28599598/uniform-neural-tissue-models-produced-on-synthetic-hydrogels-using-standard-culture-techniques
#9
Christopher Barry, Matthew T Schmitz, Nicholas E Propson, Zhonggang Hou, Jue Zhang, Bao K Nguyen, Jennifer M Bolin, Peng Jiang, Brian E McIntosh, Mitchell D Probasco, Scott Swanson, Ron Stewart, James A Thomson, Michael P Schwartz, William L Murphy
The aim of the present study was to test sample reproducibility for model neural tissues formed on synthetic hydrogels. Human embryonic stem (ES) cell-derived precursor cells were cultured on synthetic poly(ethylene glycol) (PEG) hydrogels to promote differentiation and self-organization into model neural tissue constructs. Neural progenitor, vascular, and microglial precursor cells were combined on PEG hydrogels to mimic developmental timing, which produced multicomponent neural constructs with 3D neuronal and glial organization, organized vascular networks, and microglia with ramified morphologies...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28593182/the-circadian-clock-gene-bmal1-coordinates-intestinal%C3%A2-regeneration
#10
Kyle Stokes, Abrial Cooke, Hanna Chang, David R Weaver, David T Breault, Phillip Karpowicz
BACKGROUND & AIMS: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28559141/establishment-of-a-refined-culture-method-for-rat-colon-organoids
#11
Hiroyuki Isshiki, Yoshiaki Arimura, Kanna Nagaishi, Kentaro Kawakami, Kei Onodera, Kentaro Yamashita, Yasuyoshi Naishiro, Mineko Fujimiya, Kohzoh Imai, Yasuhisa Shinomura
BACKGROUND: Methods for the artificial three-dimensional (3D) culture of mouse and human small-intestinal and large-intestinal stem cells have been established with CD24(+) or Paneth cell niches. In contrast, no studies have established stable 3D culture for rat colon stem cells. In this study, we established an advanced method for efficient rat colonic stem cell culture. METHODS: Using various tissue homogenates, we investigated the colonic organoid forming capacity under the TMDU protocol immediately adjacent to Ootani's 3D culture assembly in the same culture dish...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28550311/organoid-based-epithelial-to-mesenchymal-transition-oemt-model-from-an-intestinal-fibrosis-perspective
#12
Soojung Hahn, Myeong-Ok Nam, Jung Hyun Noh, Dong Hyeon Lee, Hyun Wook Han, Duk Hwan Kim, Ki Baik Hahm, Sung Pyo Hong, Jun-Hwan Yoo, Jongman Yoo
The current in vitro or in vivo intestinal fibrosis models have many limitations. Recent advancements in the isolation and culturing of organoids has led to development of various three-dimensional (3D) intestinal disease models with in vivo physiology. In this study, we generated an organoid-based epithelial to mesenchymal transition (OEMT) model, which could be used as a novel intestinal fibrosis model. Intestinal epithelial organoids (IEOs) were isolated and cultured from the small intestines of normal mice...
May 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28550196/il-6-signaling-regulates-small-intestinal-crypt-homeostasis
#13
Victoria Jeffery, Andrew J Goldson, Jack R Dainty, Marcello Chieppa, Anastasia Sobolewski
Gut homeostasis is a tightly regulated process requiring finely tuned complex interactions between different cell types, growth factors, or cytokines and their receptors. Previous work has implicated a role for IL-6 and mucosal immune cells in intestinal regeneration following injury and in promoting inflammation and cancer. We hypothesized that IL-6 signaling could also modulate crypt homeostasis. Using mouse in vitro crypt organoid and in vivo models, this study first demonstrated that exogenous IL-6 promoted crypt organoid proliferation and increased stem cell numbers through pSTAT3 activation in Paneth cells...
May 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28512643/diagnostic-and-research-aspects-of-small-intestinal-disaccharidases-in-coeliac-disease
#14
REVIEW
Tanja Šuligoj, Paul J Ciclitira, Borut Božič
Disaccharidases (DS) are brush border enzymes embedded in the microvillous membrane of small intestinal enterocytes. In untreated coeliac disease (CD), a general decrease of DS activities is seen. This manuscript reviews different aspects of DS activities in CD: their utility in the diagnosis and their application to in vitro toxicity testing. The latter has never been established in CD research. However, with the recent advances in small intestinal organoid techniques, DS might be employed as a biomarker for in vitro studies...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28510488/distinct-effects-of-growth-hormone-and-glutamine-on-activation-of-intestinal-stem-cells
#15
Yun Chen, Sheng-Hong Tseng, Chao-Ling Yao, Chuan Li, Ya-Hui Tsai
BACKGROUND: For patients with short bowel syndrome under parenteral nutrition support, growth hormone (GH) and glutamine (GLN) have been found to help the growth of intestinal mucosa. In this research, we studied the effects of GH and GLN on intestinal stem cells (ISCs). METHODS: The in vitro and in vivo effects of GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form organoids in a Matrigel culture system. The expression levels of stemness and differentiation markers in ISCs and organoids were assessed using quantitative real-time polymerase chain reaction, immunofluorescence assay, and immunohistochemistry staining...
May 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28507600/insights-into-the-role-of-the-intestinal-microbiota-in-colon-cancer
#16
REVIEW
Sofia Oke, Alberto Martin
The intestinal microbiota consists of a dynamic organization of bacteria, viruses, archaea, and fungal species essential for maintaining gut homeostasis and protecting the host against pathogenic invasion. When dysregulated, the intestinal microbiota can contribute to colorectal cancer development. Though the microbiota is multifaceted in its ability to induce colorectal cancer, this review will focus on the capability of the microbiota to induce colorectal cancer through the modulation of immune function and the production of microbial-derived metabolites...
May 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28498614/hepatic-uptake-of-conjugated-bile-acids-is-mediated-by-both-ntcp-and-oatps-and-modulated-by-intestinal-sensing-of-plasma-bile-acid-levels-in-mice
#17
Davor Slijepcevic, Reinout L P Roscam Abbing, Takeshi Katafuchi, Antje Blank, Joanne M Donkers, Stéphanie van Hoppe, Dirk R de Waart, Dagmar Tolenaars, Jonathan H M van der Meer, Manon Wildenberg, Ulrich Beuers, Ronald P J Oude Elferink, Alfred H Schinkel, Stan F J van de Graaf
BACKGROUND & AIMS: The Na(+) -taurocholate cotransporting polypeptide (NTCP/SLC10A1) is believed to be pivotal for hepatic uptake of conjugated bile acids. However, plasma bile acid levels are normal in a subset of NTCP knockout mice and in mice treated with myrcludex B, a specific NTCP inhibitor. Here, we elucidated which transport proteins mediate the hepatic uptake of conjugated bile acids and demonstrated intestinal sensing of elevated bile acid levels in plasma in mice. METHODS: Mice or healthy volunteers were treated with myrcludex B...
May 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28484457/type-i-and-type-iii-interferons-display-different-dependency-on-mitogen-activated-protein-kinases-to-mount-an-antiviral-state-in-the-human-gut
#18
Kalliopi Pervolaraki, Megan L Stanifer, Stephanie Münchau, Lynnsey A Renn, Dorothee Albrecht, Stefan Kurzhals, Elena Senís, Dirk Grimm, Jutta Schröder-Braunstein, Ronald L Rabin, Steeve Boulant
Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28483523/effect-of-essential-amino-acids-on-enteroids-methionine-deprivation-suppresses-proliferation-and-affects-differentiation-in-enteroid-stem-cells
#19
Yuki Saito, Ken Iwatsuki, Hikaru Hanyu, Natsuki Maruyama, Eitaro Aihara, Miki Tadaishi, Makoto Shimizu, Kazuo Kobayashi-Hattori
We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28475412/pi3k-akt-mtor-axis-sustains-rotavirus-infection-via-the-4e-bp1-mediated-autophagy-pathway-and-represents-an-antiviral-target
#20
Yuebang Yin, Wen Dang, Xinying Zhou, Lei Xu, Wenshi Wang, Wanlu Cao, Sunrui Chen, Junhong Su, Xuepeng Cai, Shaobo Xiao, Maikel P Peppelenbosch, Qiuwei Pan
Rotavirus infection is a major cause of severe dehydrating diarrhea in infants younger than 5 y old and in particular cases of immunocompromised patients irrespective to the age of the patients. Although vaccines have been developed, antiviral therapy is an important complement that cannot be substituted. Because of the lack of specific approved treatment, it is urgent to facilitate the cascade of further understanding of the infection biology, identification of druggable targets and the final development of effective antiviral therapies...
May 5, 2017: Virulence
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