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https://www.readbyqxmd.com/read/28211365/converging-biofabrication-and-organoid-technologies-the-next-frontier-in-hepatic-and-intestinal-tissue-engineering
#1
Kerstin Schneeberger, Bart Spee, Pedro Costa, Norman Sachs, Hans Clevers, Jos Malda
Adult tissue stem cells can form self-organizing 3D organoids in vitro. Organoids resemble small units of their organ of origin and have great potential for tissue engineering, as well as models of disease. However, current culture technology limits the size, architecture and complexity of organoids. Here, we review the establishment of intestinal and hepatic organoids and discuss how the convergence of organoids and biofabrication technologies can help overcome current limitations, and thereby further advance the translational application of organoids in tissue engineering and regenerative medicine...
February 17, 2017: Biofabrication
https://www.readbyqxmd.com/read/28195397/alcohol-injury-damages-intestinal-stem-cells
#2
Rong Lu, Robin M Voigt, Yongguo Zhang, Ikuko Kato, Yinglin Xia, Christopher B Forsyth, Ali Keshavarzian, Jun Sun
BACKGROUND: Alcohol consumption is associated with intestinal injury including intestinal leakiness and the risk of developing progressive gastrointestinal cancer. Alcoholics have disruption of intestinal barrier dysfunction that persists weeks after stopping alcohol intake and this occurs in spite of the fact that intestinal epithelial cells turn over every 3-5 days. The renewal and functional regulation of the intestinal epithelium largely relies on intestinal stem cells (ISCs). Chronic inflammation and tissue damage in the intestine can injure stem cells including accumulation of mutations that may result in ISC dysfunction and transformation...
February 14, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28191783/concise-review-the-potential-use-of-intestinal-stem-cells-to-treat-patients-with-intestinal-failure
#3
Sung Noh Hong, James C Y Dunn, Matthias Stelzner, Martín G Martín
Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28179500/ninein-is-essential-for-apico-basal-microtubule-formation-and-clip-170-facilitates-its-redeployment-to-non-centrosomal-microtubule-organizing-centres
#4
Deborah A Goldspink, Chris Rookyard, Benjamin J Tyrrell, Jonathan Gadsby, James Perkins, Elizabeth K Lund, Niels Galjart, Paul Thomas, Tom Wileman, Mette M Mogensen
Differentiation of columnar epithelial cells involves a dramatic reorganization of the microtubules (MTs) and centrosomal components into an apico-basal array no longer anchored at the centrosome. Instead, the minus-ends of the MTs become anchored at apical non-centrosomal microtubule organizing centres (n-MTOCs). Formation of n-MTOCs is critical as they determine the spatial organization of MTs, which in turn influences cell shape and function. However, how they are formed is poorly understood. We have previously shown that the centrosomal anchoring protein ninein is released from the centrosome, moves in a microtubule-dependent manner and accumulates at n-MTOCs during epithelial differentiation...
February 2017: Open Biology
https://www.readbyqxmd.com/read/28174963/p002-inhibition-of-axl-signaling-by-bgb324-reduces-fibrogenesis-in-human-intestinal-cells-and-human-intestinal-organoids
#5
C Steiner, E Rodansky, L A Johnson, S Huang, J Spence, P D Higgins
No abstract text is available yet for this article.
February 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28174251/a-process-engineering-approach-to-increase-organoid-yield
#6
Natasha Arora, Jasmin Imran Alsous, Jacob W Guggenheim, Michael Mak, Jorge Munera, James M Wells, Roger D Kamm, H Harry Asada, Stanislav Y Shvartsman, Linda G Griffith
Temporal manipulation of the in vitro environment and growth factors can direct differentiation of human pluripotent stem cells into organoids, aggregates with multiple tissue-specific cell types and three-dimensional structure mimicking native organs. A mechanistic understanding of early organoid formation is essential for improving the robustness of these methods, which is necessary prior to use in drug development and regenerative medicine. We investigated intestinal organoid emergence, focusing on measurable parameters of hindgut spheroids, the intermediate step between definitive endoderm and mature organoids...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28159868/using-murine-derived-primary-intestinal-enteroids-for-studies-of-dietary-triglyceride-absorption-and-lipoprotein-synthesis-and-to-determine-the-role-of-intestine-specific-apoc-iii
#7
Javeed J Jattan, Cayla N Rodia, Diana Li, Adama C Diakhate, Hongli Dong, Amy M Bataille, Noah F Shroyer, Alison B Kohan
Since its initial report in 2009, the intestinal enteroid culture system has been a powerful tool used to study stem cell biology and development in the gastrointestinal tract. However, a major question is whether enteroids retain intestinal function and physiology. There have been significant contributions describing ion transport physiology of human intestinal organoid cultures, as well as physiology of gastric organoids, but critical studies on dietary fat absorption and chylomicron synthesis in primary intestinal enteroids have not been undertaken...
February 3, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28157495/map-k-ing-the-path-to-stem-cell-quiescence-and-the-elusive-enteroendocrine-cell
#8
Simon J Leedham
The existence and interaction of proliferating and quiescent intestinal stem cells have been debated since their discovery in the 1970s. In this issue of Cell Stem Cell, using murine intestinal organoids, Basak et al. (2017) induce stem cell quiescence by selective inhibition of EGF/MAPK signaling and define culture conditions that direct differentiation to the enteroendocrine lineage.
February 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28151470/adipocytes-activate-mitochondrial-fatty-acid-oxidation-and-autophagy-to-promote-tumor-growth-in-colon-cancer
#9
Yang-An Wen, Xiaopeng Xing, Jennifer W Harris, Yekaterina Y Zaytseva, Mihail I Mitov, Dana L Napier, Heidi L Weiss, B Mark Evers, Tianyan Gao
Obesity has been associated with increased incidence and mortality of a wide variety of human cancers including colorectal cancer. However, the molecular mechanism by which adipocytes regulate the metabolism of colon cancer cells remains elusive. In this study, we showed that adipocytes isolated from adipose tissues of colon cancer patients have an important role in modulating cellular metabolism to support tumor growth and survival. Abundant adipocytes were found in close association with invasive tumor cells in colon cancer patients...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28123937/fermentable-carbohydrate-stimulates-ffar2-dependent-colonic-pyy-cell-expansion%C3%A2-to%C3%A2-increase-satiety
#10
Lucy Brooks, Alexander Viardot, Anastasia Tsakmaki, Emilie Stolarczyk, Jane K Howard, Patrice D Cani, Amandine Everard, Michelle L Sleeth, Arianna Psichas, Jelena Anastasovskaj, Jimmy D Bell, Kim Bell-Anderson, Charles R Mackay, Mohammad A Ghatei, Stephen R Bloom, Gary Frost, Gavin A Bewick
OBJECTIVE: Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. METHODS: Wild-type or Ffar2(-/-) mice were fed an inulin supplemented or control diet...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28109091/-effect-of-deoxycholic-acid-intervention-on-growth-of-ileum-organoids-derived-from-c57bl-6-mice
#11
Li-Hong Lou, Yue Zeng, Hui Zhou, Ying-Ying Lu, Xing-Peng Wang
OBJECTIVE: To establish a culture system for mouse intestinal organoids and investigate the effect of deoxycholic acid (DCA) on organoids growth. METHODS: The terminal ileum was collected from 8-month-old C57BL<6 mice. The tissue blocks were treated with EDTA and the crypts were collected and embedded in Matrigel Matrix. Orgnoids growth and buddings were observed in the control group, anhydrous alcohol group, short-term (2 days) 100 µmol<L DCA treatment group, and long-term (10 days) 10 µmol<L DCA treatment group; the orgnoids were further cultured for 10 days after removal of DCA from the medium and observed for orgnoids growth and buddings...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28098247/c-jun-n-terminal-kinase-2-promotes-enterocyte-survival-and-goblet-cell-differentiation-in-the-inflamed-intestine
#12
A D Mandić, E Bennek, J Verdier, K Zhang, S Roubrocks, R J Davis, B Denecke, N Gassler, K Streetz, A Kel, M Hornef, F J Cubero, C Trautwein, G Sellge
c-Jun N-terminal kinases (JNKs) contribute to immune signaling but their functional role during intestinal mucosal inflammation has remained ill defined. Using genetic mouse models, we characterized the role of JNK1 and JNK2 during homeostasis and acute colitis. Epithelial apoptosis, regeneration, differentiation, and barrier function were analyzed in intestinal epithelium-specific (ΔIEC) or complete JNK1 and bone marrow chimeric or complete JNK2 deficient mice as well as double-knockout animals (JNK1(ΔIEC)JNK2(-/-)) during homeostasis and acute dextran sulfate sodium (DSS)-induced colitis...
January 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28097227/a-xenogeneic-free-system-generating-functional-human-gut-organoids-from-pluripotent-stem-cells
#13
Hajime Uchida, Masakazu Machida, Takumi Miura, Tomoyuki Kawasaki, Takuya Okazaki, Kengo Sasaki, Seisuke Sakamoto, Noriaki Ohuchi, Mureo Kasahara, Akihiro Umezawa, Hidenori Akutsu
Functional intestines are composed of cell types from all 3 primary germ layers and are generated through a highly orchestrated and serial developmental process. Directed differentiation of human pluripotent stem cells (hPSCs) has been shown to yield gut-specific cell types; however, these structures do not reproduce critical functional interactions between cell types of different germ layers. Here, we developed a simple protocol for the generation of mature functional intestinal organoids from hPSCs under xenogeneic-free conditions...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28094771/orphan-gpr182-suppresses-erk-mediated-intestinal-proliferation-during-regeneration-and-adenoma-formation
#14
Daniel O Kechele, R Eric Blue, Bailey Zwarycz, Scott T Espenschied, Amanda T Mah, Marni B Siegel, Charles M Perou, Shengli Ding, Scott T Magness, P Kay Lund, Kathleen M Caron
Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28092415/the-cluster-micrornas-mir-194-and-mir-215-suppress-the-tumorigenicity-of-intestinal-tumor-organoids
#15
Toshiaki Nakaoka, Yoshimasa Saito, Yuriko Shimamoto, Toshihide Muramatsu, Masaki Kimura, Yae Kanai, Hidetsugu Saito
Tumor stem cells with self-renewal and multipotent capacity play critical roles in the initiation and progression of cancer. Recently, a new 3D culture system known as organoid culture has been developed, allowing Lgr5-positive stem cells to form organoids that resemble the properties of original tissues. Here we established organoids derived from intestinal tumors of Apc(min/+) mice and normal intestinal epithelia of C57BL/6J mice and investigated the roles of microRNAs (miRNAs) in intestinal tumor organoids...
January 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/28078320/lgr4-and-lgr5-function-redundantly-during-human-endoderm-differentiation
#16
Yu-Hwai Tsai, David R Hill, Namit Kumar, Sha Huang, Alana M Chin, Briana R Dye, Melinda S Nagy, Michael P Verzi, Jason R Spence
BACKGROUND & AIMS: The Lgr family of transmembrane proteins (Lgr4, 5, 6) act as functional receptors for R-spondin proteins (Rspo 1, 2, 3, 4), and potentiate Wnt signaling in different contexts. Lgr5 is arguably the best characterized of the Lgr family members in a number of adult and embryonic contexts in mice. However, the function of LGR family members in early embryonic development is unclear, and has not been explored during human development or tissue differentiation in detail. METHODS: We interrogated the function and expression of LGR family members using human pluripotent stem cell-derived tissues including definitive endoderm, mid/hindgut, and intestinal organoids...
September 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28074039/cd34-mesenchymal-cells-are-a-major-component-of-the-intestinal-stem-cells-niche-at-homeostasis-and-after-injury
#17
Igor Stzepourginski, Giulia Nigro, Jean-Marie Jacob, Sophie Dulauroy, Philippe J Sansonetti, Gérard Eberl, Lucie Peduto
The intestinal epithelium is continuously renewed by intestinal epithelial stem cells (IESCs) positioned at the base of each crypt. Mesenchymal-derived factors are essential to maintain IESCs; however, the cellular composition and development of such mesenchymal niche remains unclear. Here, we identify pericryptal CD34(+) Gp38(+) αSMA(-) mesenchymal cells closely associated with Lgr5(+) IESCs. We demonstrate that CD34(+) Gp38(+) cells are the major intestinal producers of the niche factors Wnt2b, Gremlin1, and R-spondin1, and are sufficient to promote maintenance of Lgr5(+) IESCs in intestinal organoids, an effect mainly mediated by Gremlin1...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28072391/braf-v600e-cooperates-with-cdx2-inactivation-to-promote-serrated-colorectal-tumorigenesis
#18
Naoya Sakamoto, Ying Feng, Carmine Stolfi, Yuki Kurosu, Maranne Green, Jeffry Lin, Megan E Green, Kazuhiro Sentani, Wataru Yasui, Martin McMahon, Karin M Hardiman, Jason R Spence, Nobukatsu Horita, Joel K Greenson, Rork Kuick, Kathleen R Cho, Eric R Fearon
While 20-30% of colorectal cancers (CRCs) may arise from precursors with serrated glands, only 8-10% of CRCs manifest serrated morphology at diagnosis. Markers for distinguishing CRCs arising from 'serrated' versus 'conventional adenoma' precursors are lacking. We studied 36 human serrated CRCs and found CDX2 loss or BRAF mutations in ~60% of cases and often together (p=0.04). CDX2(Null)/BRAF(V600E) expression in adult mouse intestinal epithelium led to serrated morphology tumors (including carcinomas) and BRAF(V600E) potently interacted with CDX2 silencing to alter gene expression...
January 10, 2017: ELife
https://www.readbyqxmd.com/read/28061355/hacking-the-matrix
#19
Michael Czerwinski, Jason R Spence
Recently in Nature, Gjorevski et al. (2016) describe a fully defined synthetic hydrogel that mimics the extracellular matrix to support in vitro growth of intestinal stem cells and organoids. The hydrogel allows exquisite control over the chemical and physical in vitro niche and enables identification of regulatory properties of the matrix.
January 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28061353/created-of-warm-blood-and-nerves-restoring-an-enteric-nervous-system-in-organoids
#20
Christopher R Schlieve, Tracy C Grikscheit
The enteric nervous system (ENS) regulates numerous gastrointestinal functions, including epithelial barrier permeability and motility. In a recent Nature Medicine study, Workman et al. (2016) propose a method for introducing human pluripotent stem cell-derived enteric neural crest cells into developing human intestinal organoids, thereby restoring ENS cell types and contractile function.
January 5, 2017: Cell Stem Cell
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