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fetal AND organoid AND intestinal

Renée R C E Schreurs, Martin E Baumdick, Adrian F Sagebiel, Max Kaufmann, Michal Mokry, Paul L Klarenbeek, Nicola Schaltenberg, Fenja L Steinert, Jorik M van Rijn, Agata Drewniak, Sarah-May M L The, Roel Bakx, Joep P M Derikx, Niek de Vries, Willemijn E Corpeleijn, Steven T Pals, Nicola Gagliani, Manuel A Friese, Sabine Middendorp, Edward E S Nieuwenhuis, Konrad Reinshagen, Teunis B H Geijtenbeek, Johannes B van Goudoever, Madeleine J Bunders
Although the fetal immune system is considered tolerogenic, preterm infants can suffer from severe intestinal inflammation, including necrotizing enterocolitis (NEC). Here, we demonstrate that human fetal intestines predominantly contain tumor necrosis factor-α (TNF-α)+ CD4+ CD69+ T effector memory (Tem) cells. Single-cell RNA sequencing of fetal intestinal CD4+ T cells showed a T helper 1 phenotype and expression of genes mediating epithelial growth and cell cycling. Organoid co-cultures revealed a dose-dependent, TNF-α-mediated effect of fetal intestinal CD4+ T cells on intestinal stem cell (ISC) development, in which low T cell numbers supported epithelial development, whereas high numbers abrogated ISC proliferation...
February 5, 2019: Immunity
Meghan M Capeling, Michael Czerwinski, Sha Huang, Yu-Hwai Tsai, Angeline Wu, Melinda S Nagy, Benjamin Juliar, Nambirajan Sundaram, Yang Song, Woojin M Han, Shuichi Takayama, Eben Alsberg, Andres J Garcia, Michael Helmrath, Andrew J Putnam, Jason R Spence
Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture...
December 19, 2018: Stem Cell Reports
Marit Navis, Tânia Martins Garcia, Ingrid B Renes, Jacqueline Lm Vermeulen, Sander Meisner, Manon E Wildenberg, Gijs R van den Brink, Ruurd M van Elburg, Vanesa Muncan
During the suckling-to-weaning transition, the intestinal epithelium matures, allowing digestion of solid food. Transplantation experiments with rodent fetal epithelium into subcutaneous tissue of adult animals suggest that this transition is intrinsically programmed and occurs in the absence of dietary or hormonal signals. Here, we show that organoids derived from mouse primary fetal intestinal epithelial cells express markers of late fetal and neonatal development. In a stable culture medium, these fetal epithelium-derived organoids lose all markers of neonatal epithelium and start expressing hallmarks of adult epithelium in a time frame that mirrors epithelial maturation in vivo In vitro postnatal development of the fetal-derived organoids accelerates by dexamethasone, a drug used to accelerate intestinal maturation in vivo Together, our data show that organoids derived from fetal epithelium undergo suckling-to-weaning transition, that the speed of maturation can be modulated, and that fetal organoids can be used to model the molecular mechanisms of postnatal epithelial maturation...
December 10, 2018: EMBO Reports
Yanchun Liu, Yijie Wang, Jason Chakroff, Jed Johnson, Aidan Farrell, Gail E Besner
This study compared side-by-side the impact of donor age on the production of tissue-engineered small intestine (TESI). Each age represents a specific period of life: E18 for fetuses, 5-day-old pups for neonates, 21-day-old rats for weanlings, and 6-week-old rats for adults. The TESI produced was compared macroscopically and microscopically. The mechanism(s) contributing to the differences observed was explored by detecting proliferating cells in the TESI and by analyzing intestinal stem cell gene expression in donor cells...
November 7, 2018: Tissue Engineering. Part A
Xiaogang Hou, David F Chang, Andrew Trecartin, Erik R Barthel, Christopher R Schlieve, Mark R Frey, Kathryn L Fowler, Tracy C Grikscheit
NEW FINDINGS: What is the central question of this study? Tissue-engineered small intestine was previously generated in vivo by immediate implantation of organoid units derived from both mouse and human donor intestine. Although immediate transplantation of organoid units into patients shows promise as a potential future therapy, some critically ill patients might require delayed transplantation. What is the main finding and its importance? Unlike enteroids, which consist of isolated intestinal crypts, short- and long-term cultured organoid units are composed of epithelial and mesenchymal cells derived from mouse or human intestine...
December 2018: Experimental Physiology
Stefania Senger, Laura Ingano, Rachel Freire, Antony Anselmo, Weishu Zhu, Ruslan Sadreyev, William Allan Walker, Alessio Fasano
Background & Aims: Untreated necrotizing enterocolitis (NEC) can lead to massive inflammation resulting in intestinal necrosis with a high mortality rate in preterm infants. Limited access to human samples and relevant experimental models have hampered progress in NEC pathogenesis. Earlier evidence has suggested that bacterial colonization of an immature and developing intestine can lead to an abnormally high inflammatory response to bacterial bioproducts. The aim of our study was to use human fetal organoids to gain insights into NEC pathogenesis...
2018: Cellular and Molecular Gastroenterology and Hepatology
Manasa Srivillibhuthur, Bailey N Warder, Natalie H Toke, Pooja P Shah, Qiang Feng, Nan Gao, Edward M Bonder, Michael P Verzi
During development, the embryo transitions from a metabolism favoring glycolysis to a metabolism favoring mitochondrial respiration. How metabolic shifts regulate developmental processes, or how developmental processes regulate metabolic shifts, remains unclear. To test the requirement of mitochondrial function in developing endoderm-derived tissues, we genetically inactivated the mitochondrial transcription factor, Tfam, using the Shh-Cre driver. Tfam mutants did not survive postnatally, exhibiting defects in lung development...
July 15, 2018: Developmental Biology
Salwa Khedr, Tarek Jazaerly, Stefan Kostadinov
We report an unusual case of fully developed fetal intestinal segment(s) within a nodule on the chorionic plate of the placenta of a 27-year-old female patient at 37 weeks gestation with spontaneous vaginal delivery. Gross examination of the placenta revealed a chorionic plate nodule near the insertion of the umbilical cord, which, upon microscopic evaluation, raised the differential diagnostic possibilities of placental teratoma, vitelline/omphalomesenteric duct anomaly, and intestinal organoid differentiation...
December 2017: Journal of Pediatric Genetics
Judith Kraiczy, Komal M Nayak, Kate J Howell, Alexander Ross, Jessica Forbester, Camilla Salvestrini, Roxana Mustata, Sally Perkins, Amanda Andersson-Rolf, Esther Leenen, Anke Liebert, Ludovic Vallier, Philip C Rosenstiel, Oliver Stegle, Gordon Dougan, Robert Heuschkel, Bon-Kyoung Koo, Matthias Zilbauer
OBJECTIVE: Human intestinal epithelial organoids (IEOs) are increasingly being recognised as a highly promising translational research tool. However, our understanding of their epigenetic molecular characteristics and behaviour in culture remains limited. DESIGN: We performed genome-wide DNA methylation and transcriptomic profiling of human IEOs derived from paediatric/adult and fetal small and large bowel as well as matching purified human gut epithelium. Furthermore, organoids were subjected to in vitro differentiation and genome editing using CRISPR/Cas9 technology...
November 15, 2017: Gut
Dongsheng Zhang, Ming Tan, Weiming Zhong, Ming Xia, Pengwei Huang, Xi Jiang
Through pluripotent stem cell (PSC) technology, human intestinal organoids (HIOs) with remarkably similarity to the fetal intestine in cellular composition, architecture, and absorptive/secretory functions have been successfully developed, providing a useful in vitro model system to study the structure and function of human congenital gut and intestinally related diseases. We report here the usefulness of HIOs as a model system to study intestinal carbohydrate expression, virus-host interaction, and replication of human noroviruses (huNoVs)...
October 3, 2017: Scientific Reports
Shizuka Miura, Atsushi Suzuki
Intestinal organoids hold great promise as a valuable tool for studying and treating intestinal diseases. The currently available sources of human intestinal organoids, tissue fragments or pluripotent stem cells, involve invasive procedures or complex differentiation protocols, respectively. Here, we show that a set of four transcription factors, Hnf4α, Foxa3, Gata6, and Cdx2, can directly reprogram mouse fibroblasts to acquire the identity of fetal intestine-derived progenitor cells (FIPCs). These induced FIPCs (iFIPCs) form spherical organoids that develop into adult-type budding organoids containing cells with intestinal stem cell properties...
October 5, 2017: Cell Stem Cell
Megan Aurora, Jason R Spence
In vitro human pluripotent stem cell (hPSC) derived tissues are excellent models to study certain aspects of normal human development. Current research in the field of hPSC derived tissues reveals these models to be inherently fetal-like on both a morphological and gene expression level. In this review we briefly discuss current methods for differentiating lung and intestinal tissue from hPSCs into individual 3-dimensional units called organoids. We discuss how these methods mirror what is known about in vivo signaling pathways of the developing embryo...
December 15, 2016: Developmental Biology
Stacy R Finkbeiner, David R Hill, Christopher H Altheim, Priya H Dedhia, Matthew J Taylor, Yu-Hwai Tsai, Alana M Chin, Maxime M Mahe, Carey L Watson, Jennifer J Freeman, Roy Nattiv, Matthew Thomson, Ophir D Klein, Noah F Shroyer, Michael A Helmrath, Daniel H Teitelbaum, Peter J Dempsey, Jason R Spence
Human intestinal organoids (HIOs) are a tissue culture model in which small intestine-like tissue is generated from pluripotent stem cells. By carrying out unsupervised hierarchical clustering of RNA-sequencing data, we demonstrate that HIOs most closely resemble human fetal intestine. We observed that genes involved in digestive tract development are enriched in both fetal intestine and HIOs compared to adult tissue, whereas genes related to digestive function and Paneth cell host defense are expressed at higher levels in adult intestine...
June 3, 2015: Stem Cell Reports
Julie M Cramer, Timothy Thompson, Albert Geskin, William LaFramboise, Eric Lagasse
The intestine is composed of an epithelial layer containing rapidly proliferating cells that mature into two regions, the small and the large intestine. Although previous studies have identified stem cells as the cell-of-origin for intestinal epithelial cells, no studies have directly compared stem cells derived from these anatomically distinct regions. Here, we examine intrinsic differences between primary epithelial cells isolated from human fetal small and large intestine, after in vitro expansion, using the Wnt agonist R-spondin 2...
2015: PloS One
Birgit Andrée, Katharina Bela, Tibor Horvath, Marco Lux, Robert Ramm, Letizia Venturini, Anatol Ciubotaru, Robert Zweigerdt, Axel Haverich, Andres Hilfiker
Generating cellularized 3D constructs with clinical relevant dimensions is challenged by nutrition supply. This is of utmost importance for cardiac tissue engineering, since cardiomyocytes are extremely sensitive to malnutrition and hypoxia in vitro and after implantation. To develop a perfusable myocardial patch, we have focused on seeding a decellularized biological vascularized matrix (BioVaM) with endothelial cells. BioVaM is produced by decellularization of porcine small intestinal segments with preserved arterial and venous pedicles, which can be connected to a perfusion system in vitro or the host vasculature in vivo...
2014: Basic Research in Cardiology
Marc Leushacke, Nick Barker
Limited pools of resident adult stem cells are critical effectors of epithelial renewal in the intestine throughout life. Recently, significant progress has been made regarding the isolation and in vitro propagation of fetal and adult intestinal stem cells in mammals. It is now possible to generate ever-expanding, three-dimensional epithelial structures in culture that closely parallel the in vivo epithelium of the intestine. Growing such organotypic epithelium ex vivo facilitates a detailed description of endogenous niche factors or stem-cell characteristics, as they can be monitored in real time...
August 2014: Gut
Roxana C Mustata, Gabriela Vasile, Valeria Fernandez-Vallone, Sandra Strollo, Anne Lefort, Frédérick Libert, Daniel Monteyne, David Pérez-Morga, Gilbert Vassart, Marie-Isabelle Garcia
Immortal spheroids were generated from fetal mouse intestine using the culture system initially developed to culture organoids from adult intestinal epithelium. Spheroid proportion progressively decreases from fetal to postnatal period, with a corresponding increase in production of organoids. Like organoids, spheroids show Wnt-dependent indefinite self-renewing properties but display a poorly differentiated phenotype reminiscent of incompletely caudalized progenitors. The spheroid transcriptome is strikingly different from that of adult intestinal stem cells, with minimal overlap of Wnt target gene expression...
October 31, 2013: Cell Reports
Robert P Fordham, Shiro Yui, Nicholas R F Hannan, Christoffer Soendergaard, Alison Madgwick, Pawel J Schweiger, Ole H Nielsen, Ludovic Vallier, Roger A Pedersen, Tetsuya Nakamura, Mamoru Watanabe, Kim B Jensen
Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a...
December 5, 2013: Cell Stem Cell
Hong Chen, Stefanie Wiedmer, Sacha Hanig, Rolf Entzeroth, Michael Kurth
The in vitro production of gametocytes and oocysts of the apicomplexan parasite genus Eimeria is still a challenge in coccidiosis research. Until today, an in vitro development of gametocytes or oocysts had only been shown in some Eimeria species. For several mammalian Eimeria species, partial developments could be achieved in different cell types, but a development up to gametocytes or oocysts is still lacking. This study compares several permanent cell lines with primary fetal cells of the black rat (Rattus norvegicus) concerning the qualitative in vitro development of the rat parasite Eimeria nieschulzi...
2013: Journal of Parasitology Research
Daniel E Levin, Erik R Barthel, Allison L Speer, Frédéric G Sala, Xiaogang Hou, Yasuhiro Torashima, Tracy C Grikscheit
PURPOSE: Tissue-engineered small intestine (TESI) represents a potential cure for short bowel syndrome (SBS). We previously reported full-thickness intestine formation using an organoid units-on-scaffold approach in rodent and swine models. Transplanted intestinal xenografts have been documented to survive from human fetal tissue but not from postnatal tissue. We now present the first report of human TESI from postnatal tissue. METHODS: Organoid units (OU) were prepared from human small bowel resection specimens, loaded onto biodegradable scaffolds and implanted into NOD/SCID gamma chain-deficient mice...
January 2013: Journal of Pediatric Surgery
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