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Stem cell intestinal

Joo-Hung Park, Jeong-Min Lee, Eun-Jin Lee, Won-Bhin Hwang, Da-Jeong Kim
Using an in vitro model of intestinal organoids derived from intestinal crypts, we examined effects of indole-3-carbinol (I3C), a phytochemical that has anticancer and aryl hydrocarbon receptor (AhR)-activating abilities and thus is sold as a dietary supplement, on the development of intestinal organoids and investigated the underlying mechanisms. I3C inhibited the in vitro development of mouse intestinal organoids. Addition of α-naphthoflavone, an AhR antagonist or AhR siRNA transfection, suppressed I3C function, suggesting that I3C-mediated interference with organoid development is AhR-dependent...
March 21, 2018: Molecules and Cells
L N Zhang, M H Li, J Zhou, Y L Zhang, X D Wei, Y P Song
No abstract text is available yet for this article.
March 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
X Chen, W H Zhai, Q L Ma, J F Yao, G Li, C Liang, E L Jiang, S Z Feng, M Z Han
No abstract text is available yet for this article.
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Qinhua Zhou, Xiaoying Hui, Wenjing Ying, Jia Hou, Wenjie Wang, Danru Liu, Ying Wang, Yeheng Yu, Jingyi Wang, Jinqiao Sun, Qian Zhang, Xiaochuan Wang
PURPOSE: Clinical diagnosis and treatment for chronic granulomatous disease (CGD) have advanced greatly in recent years. However, CGD patients in China have unique clinical features and infection spectrums, which are challenging to their caretakers. Here, we summarized the clinical characteristics, genetic features, treatment, and prognosis of CGD in a single center in Shanghai. METHODS: One hundred sixty-nine CGD patients were recruited between January 2004 and May 2017 based on clinical diagnosis...
March 20, 2018: Journal of Clinical Immunology
Gediminas Greicius, Zahra Kabiri, Kristmundur Sigmundsson, Chao Liang, Ralph Bunte, Manvendra K Singh, David M Virshup
Wnts and R-spondins (RSPOs) support intestinal homeostasis by regulating crypt cell proliferation and differentiation. Ex vivo, Wnts secreted by Paneth cells in organoids can regulate the proliferation and differentiation of Lgr5 -expressing intestinal stem cells. However, in vivo, Paneth cell and indeed all epithelial Wnt production is completely dispensable, and the cellular source of Wnts and RSPOs that maintain the intestinal stem-cell niche is not known. Here we investigated both the source and the functional role of stromal Wnts and RSPO3 in regulation of intestinal homeostasis...
March 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
D J Huels, L Bruens, M C Hodder, P Cammareri, A D Campbell, R A Ridgway, D M Gay, M Solar-Abboud, W J Faller, C Nixon, L B Zeiger, M E McLaughlin, E Morrissey, D J Winton, H J Snippert, J van Rheenen, O J Sansom
Many epithelial stem cell populations follow a pattern of stochastic stem cell divisions called 'neutral drift'. It is hypothesised that neutral competition between stem cells protects against the acquisition of deleterious mutations. Here we use a Porcupine inhibitor to reduce Wnt secretion at a dose where intestinal homoeostasis is maintained despite a reduction of Lgr5+ stem cells. Functionally, there is a marked acceleration in monoclonal conversion, so that crypts become rapidly derived from a single stem cell...
March 19, 2018: Nature Communications
Peng Wei, Katja K Dove, Claire Bensard, John C Schell, Jared Rutter
Compared to their differentiated progeny, stem cells are often characterized by distinct metabolic landscapes that emphasize anaerobic glycolysis and a lower fraction of mitochondrial carbohydrate oxidation. Until recently, the metabolic program of stem cells had been thought to be a byproduct of the environment, rather than an intrinsic feature determined by the cell itself. However, new studies highlight the impact of metabolic behavior on the maintenance and function of intestinal stem cells and hair follicle stem cells...
March 16, 2018: Trends in Cell Biology
Wyatt E Lanik, Lily Xu, Cliff J Luke, Elise Z Hu, Pranjal Agrawal, Victoria S Liu, Rajesh Kumar, Alexa M Bolock, Congrong Ma, Misty Good
Human small intestinal enteroids are derived from the crypts and when grown in a stem cell niche contain all of the epithelial cell types. The ability to establish human enteroid ex vivo culture systems are important to model intestinal pathophysiology and to study the particular cellular responses involved. In recent years, enteroids from mice and humans are being cultured, passaged, and banked away for future use in several laboratories across the world. This enteroid platform can be used to test the effects of various treatments and drugs and what effects are exerted on different cell types in the intestine...
February 15, 2018: Journal of Visualized Experiments: JoVE
Alexandra K Eicher, H Matthew Berns, James M Wells
Gastric diseases, including peptic ulcer disease and gastric cancer, are highly prevalent in human beings. Despite this, the cellular biology of the stomach remains poorly understood relative to other gastrointestinal organs such as the liver, intestine, and colon. In particular, little is known about the molecular basis of stomach development and the differentiation of gastric lineages. Although animal models are useful for studying gastric development, function, and disease, there are major structural and physiological differences in human stomachs that render these models insufficient...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Sayon Basu, Nancy Gavert, Thomas Brabletz, Avri Ben-Ze'ev
Aberrant Wnt/β-catenin signaling is a common event during human colorectal cancer (CRC) development. Previously, we characterized members of the L1 family of cell adhesion receptors as targets of β-catenin-LEF1/TCF transactivation that are expressed at the invasive CRC tissue edge. Overexpression of L1 in CRC cells confers enhanced motility, tumorigenesis and liver metastasis. We identified several downstream targets of L1-mediated signaling that are considered key intestinal stem cell signature genes. Here, we investigated the involvement of ASCL2, a Wnt target gene and key determinant of intestinal stem cell state, in L1-mediated CRC progression...
March 15, 2018: Cancer Letters
Hong Jun Park, Jiye Kim, Fatema Tuj Saima, Ki-Jong Rhee, Soonjae Hwang, Moon Young Kim, Soon Koo Baik, Young Woo Eom, Hyun-Soo Kim
Inflammatory bowel disease (IBD) is an idiopathic disease caused by a dysregulated immune response to intestinal microbes in an individual with a genetic predisposition. Therefore, alleviation of inflammation is very important to treat IBD. Mesenchymal stem cells (MSCs) have been highlighted as new candidates for treating autoimmune disease based on their immunomodulatory properties. In this study, we investigated the anti-inflammatory mechanism and therapeutic effects of adipose tissue-derived MSCs (ASCs) using THP-1 macrophages and dextran sodium sulfate (DSS)-induced mice with chronic colitis...
March 15, 2018: Biochemical and Biophysical Research Communications
Domenico Umberto De Rose, Silvia Giliani, Lucia Dora Notarangelo, Vassilios Lougaris, Arnalda Lanfranchi, Daniele Moratto, Baldassarre Martire, Fernando Specchia, Alberto Tommasini, Alessandro Plebani, Raffaele Badolato
Leukocyte Adhesion Deficiency type 1 (LAD-1) is a rare primary immunodeficiency due to mutations in the gene encoding for the common β-chain of the β2 integrin family (CD18). Herein, we describe clinical manifestations and long-term complications of eight LAD-1 patients. Four LAD-1 patients were treated with hematopoietic stem cell transplantation (HSCT), while the remaining four, including two with moderate LAD-1 deficiency, received continuous antibiotic prophylaxis. Untreated patients presented numerous infections and autoimmune manifestations...
March 13, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Péter Nagy, Gyöngyvér O Sándor, Gábor Juhász
Intestinal homeostasis is maintained by tightly controlled proliferation and differentiation of tissue-resident multipotent stem cells during aging and regeneration, which ensures organismal adaptation. Here we show that autophagy is required in Drosophila intestinal stem cells to sustain proliferation, and preserves the stem cell pool. Autophagy-deficient stem cells show elevated DNA damage and cell cycle arrest during aging, and are frequently eliminated via JNK-mediated apoptosis. Interestingly, loss of Chk2, a DNA damage-activated kinase that arrests the cell cycle and promotes DNA repair and apoptosis, leads to uncontrolled proliferation of intestinal stem cells regardless of their autophagy status...
March 15, 2018: Scientific Reports
Domenique D Zomer-van Ommen, Eyleen de Poel, Evelien Kruisselbrink, Hugo Oppelaar, Annelotte M Vonk, Hettie M Janssens, Cornelis K van der Ent, Marne C Hagemeijer, Jeffrey M Beekman
BACKGROUND: New functional assays using primary human intestinal adult stem cell cultures can be valuable tools to study epithelial defects in human diseases such as cystic fibrosis. METHODS: CFTR-mediated ion transport was measured in rectal organoid-derived monolayers grown from subjects with various CFTR mutations and compared to donor-matched intestinal current measurements (ICM) in rectal biopsies and forskolin-induced swelling of rectal organoids. RESULTS: Rectal organoid-derived monolayers were generated within four days...
March 13, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Genia Dubrovsky, James C Y Dunn
PURPOSE OF REVIEW: The purpose of this review is to briefly summarize the notable structures and pathways in intestinal epithelial growth before presenting the current main areas of active research in intestinal regeneration. As a rapidly advancing field, a number of breakthroughs have recently been made related to the culture of intestinal stem cells (ISCs) and to the engineering of intestinal tissue. RECENT FINDINGS: ISCs can be derived from fibroblasts and can be cultured in hydrogels under xenogeneic-free conditions...
March 13, 2018: Current Opinion in Pediatrics
Wyatt E Lanik, Madison A Mara, Belgacem Mihi, Carolyn B Coyne, Misty Good
Studies on the intestinal epithelial response to viral infection have previously been limited by the absence of in vitro human intestinal models that recapitulate the multicellular complexity of the gastrointestinal tract. Recent technological advances have led to the development of "mini-intestine" models, which mimic the diverse cellular nature and physiological activity of the small intestine. Utilizing adult or embryonic intestinal tissue, enteroid and organoid systems, respectively, represent an opportunity to effectively model cellular differentiation, proliferation, and interactions that are specific to the specialized environment of the intestine...
March 10, 2018: Viruses
Moon Jong Kim, Bo Xia, Han Na Suh, Sung Ho Lee, Sohee Jun, Esther M Lien, Jie Zhang, Kaifu Chen, Jae-Il Park
The underlying mechanisms of how self-renewing cells are controlled in regenerating tissues and cancer remain ambiguous. PCNA-associated factor (PAF) modulates DNA repair via PCNA. Also, PAF hyperactivates Wnt/β-catenin signaling independently of PCNA interaction. We found that PAF is expressed in intestinal stem and progenitor cells (ISCs and IPCs) and markedly upregulated during intestinal regeneration and tumorigenesis. Whereas PAF is dispensable for intestinal homeostasis, upon radiation injury, genetic ablation of PAF impairs intestinal regeneration along with the severe loss of ISCs and Myc expression...
March 12, 2018: Developmental Cell
Kenyi Saito-Diaz, Hassina Benchabane, Ajit Tiwari, Ai Tian, Bin Li, Joshua J Thompson, Annastasia S Hyde, Leah M Sawyer, Jeanne N Jodoin, Eduardo Santos, Laura A Lee, Robert J Coffey, R Daniel Beauchamp, Christopher S Williams, Anne K Kenworthy, David J Robbins, Yashi Ahmed, Ethan Lee
Adenomatous polyposis coli (APC) mutations cause Wnt pathway activation in human cancers. Current models for APC action emphasize its role in promoting β-catenin degradation downstream of Wnt receptors. Unexpectedly, we find that blocking Wnt receptor activity in APC-deficient cells inhibits Wnt signaling independently of Wnt ligand. We also show that inducible loss of APC is rapidly followed by Wnt receptor activation and increased β-catenin levels. In contrast, APC2 loss does not promote receptor activation...
March 12, 2018: Developmental Cell
Saverio La Francesca, Johnathon M Aho, Matthew R Barron, Ellen W Blanco, Sherif Soliman, Lena Kalenjian, Ariel D Hanson, Elisaveta Todorova, Matthew Marsh, KaLia Burnette, Harout DerSimonian, Robert D Odze, Dennis A Wigle
Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Current reconstruction approaches are limited to utilization of an autologous conduit such as stomach, small bowel, or colon. A tissue engineered construct providing an alternative for esophageal replacement in circumferential, full thickness resection would have significant clinical applications. In the current study, we demonstrate that regeneration of esophageal tissue is feasible and reproducible in a large animal model using synthetic polyurethane electro-spun grafts seeded with autologous adipose-derived mesenchymal stem cells (aMSCs) and a disposable bioreactor...
March 7, 2018: Scientific Reports
Byoung Hyuck Kim, Hee-Won Jung, Seok Hyun Seo, Hyemi Shin, Jeanny Kwon, Jae Myoung Suh
Unwanted radiological or nuclear exposure remains a public health risk for which effective therapeutic countermeasures are lacking. Here, we evaluated the efficacy of fibroblast growth factor-2 (FGF2) in treating radiation-induced gastrointestinal syndrome (RIGS) incurred by lethal whole-body irradiation (WBI) when administered in conjunction with bone marrow transplantation (BMT). In vitro experiments indicated FGF2 treatment increased proliferation, reduced apoptosis, and upregulated AKT-GSK3β/β-catenin signaling in irradiated IEC-6 cells...
March 7, 2018: Cell Death & Disease
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