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https://www.readbyqxmd.com/read/27909243/3d-culture-models-of-tissues-under-tension
#1
REVIEW
Jeroen Eyckmans, Christopher S Chen
Cells dynamically assemble and organize into complex tissues during development, and the resulting three-dimensional (3D) arrangement of cells and their surrounding extracellular matrix in turn feeds back to regulate cell and tissue function. Recent advances in engineered cultures of cells to model 3D tissues or organoids have begun to capture this dynamic reciprocity between form and function. Here, we describe the underlying principles that have advanced the field, focusing in particular on recent progress in using mechanical constraints to recapitulate the structure and function of musculoskeletal tissues...
December 1, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27901089/a-silac-based-method-for-quantitative-proteomic-analysis-of-intestinal-organoids
#2
Alexis Gonneaud, Christine Jones, Naomie Turgeon, Dominique Lévesque, Claude Asselin, François Boudreau, François-Michel Boisvert
Organoids have the potential to bridge 3D cell culture to tissue physiology by providing a model resembling in vivo organs. Long-term growing organoids were first isolated from intestinal crypt cells and recreated the renewing intestinal epithelial niche. Since then, this technical breakthrough was applied to many other organs, including prostate, liver, kidney and pancreas. We describe here how to apply a SILAC-based quantitative proteomic approach to measure protein expression changes in intestinal organoids under different experimental conditions...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27889058/mutations-in-reep6-cause-autosomal-recessive-retinitis-pigmentosa
#3
Gavin Arno, Smriti A Agrawal, Aiden Eblimit, James Bellingham, Mingchu Xu, Feng Wang, Christina Chakarova, David A Parfitt, Amelia Lane, Thomas Burgoyne, Sarah Hull, Keren J Carss, Alessia Fiorentino, Matthew J Hayes, Peter M Munro, Ralph Nicols, Nikolas Pontikos, Graham E Holder, Chinwe Asomugha, F Lucy Raymond, Anthony T Moore, Vincent Plagnol, Michel Michaelides, Alison J Hardcastle, Yumei Li, Catherine Cukras, Andrew R Webster, Michael E Cheetham, Rui Chen
Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families...
December 1, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27882268/long-term-culture-of-intestinal-cell-progenitors-an-overview-of-their-development-application-and-associated-technologies
#4
REVIEW
Andrew J Hollins, Lee Parry
PURPOSE OF REVIEW: Long-term culture of adult progenitor cells in 3D is a recently emerging technology that inhabits the space between 2D cell lines and organ slice culture. RECENT FINDINGS: Adaptations to defined media components in the wake of advances in ES and iPS cell culture has led to the identification of conditions that maintained intestinal cell progenitors in culture. These conditions retain cellular heterogeneity of the normal or tumour tissue, and the cultures have been shown to be genetically stable, such that substantial biobanks are being created from patient derived material...
2016: Current Pathobiology Reports
https://www.readbyqxmd.com/read/27867006/intercellular-coupling-of-the-cell-cycle-and-circadian-clock-in-adult-stem-cell-culture
#5
Toru Matsu-Ura, Andrey Dovzhenok, Eitaro Aihara, Jill Rood, Hung Le, Yan Ren, Andrew E Rosselot, Tongli Zhang, Choogon Lee, Karl Obrietan, Marshall H Montrose, Sookkyung Lim, Sean R Moore, Christian I Hong
Circadian clock-gated cell division cycles are observed from cyanobacteria to mammals via intracellular molecular connections between these two oscillators. Here we demonstrate WNT-mediated intercellular coupling between the cell cycle and circadian clock in 3D murine intestinal organoids (enteroids). The circadian clock gates a population of cells with heterogeneous cell-cycle times that emerge as 12-hr synchronized cell division cycles. Remarkably, we observe reduced-amplitude oscillations of circadian rhythms in intestinal stem cells and progenitor cells, indicating an intercellular signal arising from differentiated cells governing circadian clock-dependent synchronized cell division cycles...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27859262/functional-and-prognostic-significance-of-the-genomic-amplification-of-frizzled-receptor-6-fzd6-in-breast-cancer
#6
Gabriele Corda, Gianluca Sala, Rossano Lattanzio, Manuela Iezzi, Michele Sallese, Giorgia Fragassi, Alessia Lamolinara, Hasan Mirza, Daniela Barcaroli, Sibylle Ermler, Elisabete Silva, Hemad Yasaei, Robert F Newbold, Paola Vagnarelli, Marcella Mottolese, Pier Giorgio Natali, Letizia Perracchio, Jelmar Quist, Anita Grigoriadis, Pierfrancesco Marra, Andrew N Tutt, Mauro Piantelli, Stefano Iacobelli, Vincenzo De Laurenzi, Arturo Sala
Frizzled receptors mediate Wnt ligands' signalling, which is crucially involved in regulating tissue development, differentiation and is often deregulated in cancer. In this study we found that the Wnt receptor frizzled 6 (FZD6) is frequently amplified in breast cancer, with an increased incidence in the triple negative breast cancer (TNBC) subtype. Ablation of FZD6 gene expression in mammary cancer cell lines: a) inhibited motility and invasion b) induced a more symmetric shape of organoid 3D cultures c) inhibited bone and liver metastasis in vivo...
November 9, 2016: Journal of Pathology
https://www.readbyqxmd.com/read/27844287/modeling-of-autism-using-organoid-technology
#7
REVIEW
Hwan Choi, Juhyun Song, Guiyeon Park, Jongpil Kim
Autism is a neurodevelopmental disease caused by multiple mutations during development. However, a suitable disease model to study the molecular pathway of disease onset and progression is not available. Although many studies have used human stem cells such as induced pluripotent stem cells and embryonic stem cells to investigate the disease pathogenesis, these stem cell techniques are limited in their abilities to study the pathology and mechanism of pathogenesis of neurodevelopmental diseases such as autism...
November 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27827428/pge2-is-a-direct-and-robust-mediator-of-anion-fluid-secretion-by-human-intestinal-epithelial-cells
#8
Satoru Fujii, Kohei Suzuki, Ami Kawamoto, Fumiaki Ishibashi, Toru Nakata, Tatsuro Murano, Go Ito, Hiromichi Shimizu, Tomohiro Mizutani, Shigeru Oshima, Kiichiro Tsuchiya, Tetsuya Nakamura, Akihiro Araki, Kazuo Ohtsuka, Ryuichi Okamoto, Mamoru Watanabe
Intestinal epithelial cells (IECs) play an indispensable role in maintaining body fluid balance partly through their ability to regulate anion/fluid secretion. Yet in various inflammatory gastrointestinal diseases, over-secretion of anions results in symptoms such as severe diarrhoea. Endogenous mediators, such as vasoactive intestinal peptide or prostaglandin E2 (PGE2), regulate intestinal anion/fluid secretion, but their direct effect on purified human IECs has never been described in detail. Based on a previously described intestinal organoid swelling model, we established a 3D-scanner-assisted quantification method to evaluate the anion/fluid secretory response of cultured human IECs...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27815996/human-airway-organoid-engineering-as-a-step-toward-lung-regeneration-and-disease-modeling
#9
Qi Tan, Kyoung Moo Choi, Delphine Sicard, Daniel J Tschumperlin
Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture...
January 2017: Biomaterials
https://www.readbyqxmd.com/read/27796955/a-3d-fibroblast-epithelium-co-culture-model-for-understanding-microenvironmental-role-in-branching-morphogenesis-of-the-mammary-gland
#10
Zuzana Koledova, Pengfei Lu
The mammary gland consists of numerous tissue compartments, including mammary epithelium, an array of stromal cells, and the extracellular matrix (ECM). Bidirectional interactions between the epithelium and its surrounding stroma are essential for proper mammary gland development and homeostasis, whereas their deregulation leads to developmental abnormalities and cancer. To study the relationships between the epithelium and the stroma, development of models that could recapitulate essential aspects of these interacting systems in vitro has become necessary...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27787775/the-three-dimensional-culture-of-epithelial-organoids-derived-from-embryonic-chicken-intestine
#11
Malgorzata Pierzchalska, Malgorzata Panek, Malgorzata Czyrnek, Maja Grabacka
The intestinal epithelium isolated from chicken embryos in last 3 days of development can be used to establish the 3D culture of intestinal organoids. When fragments of epithelial tissue released by incubation with EGTA (2.5 mM, 2 h) are embedded in Matrigel matrix on cell culture inserts the formation of empty spheres covered by epithelial cells is observed in first 24 h of culture. The growth and survival of organoids are supported by the addition of R-spondin 1, Noggin, and prostaglandin E2 to the culture medium...
October 28, 2016: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27783065/the-promises-and-challenges-of-human-brain-organoids-as-models-of-neuropsychiatric-disease
#12
Giorgia Quadrato, Juliana Brown, Paola Arlotta
Neuropsychiatric disorders such as autism spectrum disorder (ASD), schizophrenia (SCZ) and bipolar disorder (BPD) are of great societal and medical importance, but the complexity of these diseases and the challenges of modeling the development and function of the human brain have made these disorders difficult to study experimentally. The recent development of 3D brain organoids derived from human pluripotent stem cells offers a promising approach for investigating the phenotypic underpinnings of these highly polygenic disorders and for understanding the contribution of individual risk variants and complex genetic background to human pathology...
October 26, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27782124/wnt-and-neuregulin1-erbb-signalling-extends-3d-culture-of-hormone-responsive-mammary-organoids
#13
Thierry Jardé, Bethan Lloyd-Lewis, Mairian Thomas, Howard Kendrick, Lorenzo Melchor, Lauriane Bougaret, Peter D Watson, Kenneth Ewan, Matthew J Smalley, Trevor C Dale
The development of in vitro culture systems quantitatively and qualitatively recapitulating normal breast biology is key to the understanding of mammary gland biology. Current three-dimensional mammary culture systems have not demonstrated concurrent proliferation and functional differentiation ex vivo in any system for longer than 2 weeks. Here, we identify conditions including Neuregulin1 and R-spondin 1, allowing maintenance and expansion of mammary organoids for 2.5 months in culture. The organoids comprise distinct basal and luminal compartments complete with functional steroid receptors and stem/progenitor cells able to reconstitute a complete mammary gland in vivo...
October 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27768243/prenatal-exposure-to-environmental-factors-and-congenital-limb-defects
#14
Peter G Alexander, Karen L Clark, Rocky S Tuan
Limb congenital defects afflict approximately 0.6:1000 live births. In addition to genetic factors, prenatal exposure to drugs and environmental toxicants, represents a major contributing factor to limb defects. Examples of well-recognized limb teratogenic agents include thalidomide, warfarin, valproic acid, misoprostol, and phenytoin. While the mechanism by which these agents cause dymorphogenesis is increasingly clear, prediction of the limb teratogenicity of many thousands of as yet uncharacterized environmental factors (pollutants) remains inexact...
October 21, 2016: Birth Defects Research. Part C, Embryo Today: Reviews
https://www.readbyqxmd.com/read/27748340/organoid-culture-of-isolated-cells-from-patient-derived-tissues-with-colorectal-cancer
#15
Bing-Ying Xie, Ai-Wen Wu
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy. METHODS: We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs)...
2016: Chinese Medical Journal
https://www.readbyqxmd.com/read/27744003/neural-organoids-for-disease-phenotyping-drug-screening-and-developmental-biology-studies
#16
Brigham J Hartley, Kristen J Brennand
Human induced pluripotent stem cells (hiPSCs) can theoretically yield limitless supplies of cells fated to any cell type that comprise the human organism, making them a new tool by which to potentially overcome caveats in current biomedical research. In vitro derivation of central nervous system (CNS) cell types has the potential to provide material for drug discovery and validation, safety and toxicity assays, cell replacement therapy and the elucidation of previously unknown disease mechanisms. However, current two-dimensional (2D) CNS differentiation protocols do not faithfully recapitulate the spatial organization of heterogeneous tissue, nor the cell-cell interactions, cell-extracellular matrix interactions, or specific physiological functions generated within complex tissue such as the brain...
October 12, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27742791/neural-tube-morphogenesis-in-synthetic-3d-microenvironments
#17
Adrian Ranga, Mehmet Girgin, Andrea Meinhardt, Dominic Eberle, Massimiliano Caiazzo, Elly M Tanaka, Matthias P Lutolf
Three-dimensional organoid constructs serve as increasingly widespread in vitro models for development and disease modeling. Current approaches to recreate morphogenetic processes in vitro rely on poorly controllable and ill-defined matrices, thereby largely overlooking the contribution of biochemical and biophysical extracellular matrix (ECM) factors in promoting multicellular growth and reorganization. Here, we show how defined synthetic matrices can be used to explore the role of the ECM in the development of complex 3D neuroepithelial cysts that recapitulate key steps in early neurogenesis...
October 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27741500/modular-gag-matrices-to-promote-mammary-epithelial-morphogenesis-in%C3%A2-vitro
#18
Mirko Nowak, Uwe Freudenberg, Mikhail V Tsurkan, Carsten Werner, Kandice R Levental
Matrix systems used to study complex three-dimensional (3D) cellular processes like mammary epithelial tissue morphogenesis and tumorigenesis ex vivo often require ill-defined biological components, which lead to poor reproducibility and a lack of control over physical parameters. In this study, a well-defined, tunable synthetic biohybrid hydrogel composed of the glycosaminoglycan heparin, star-shaped poly(ethylene glycol) (starPEG), and matrix metalloproteinase- (MMP-) cleavable crosslinkers was applied to dissect the biophysical and biochemical signals promoting human mammary epithelial cell (MEC) morphogenesis...
January 2017: Biomaterials
https://www.readbyqxmd.com/read/27731367/islet-like-organoids-derived-from-human-pluripotent-stem-cells-efficiently-function-in-the-glucose-responsiveness-in-vitro-and-in-vivo
#19
Youngjin Kim, Hyeongseok Kim, Ung Hyun Ko, Youjin Oh, Ajin Lim, Jong-Woo Sohn, Jennifer H Shin, Hail Kim, Yong-Mahn Han
Insulin secretion is elaborately modulated in pancreatic ß cells within islets of three-dimensional (3D) structures. Using human pluripotent stem cells (hPSCs) to develop islet-like structures with insulin-producing ß cells for the treatment of diabetes is challenging. Here, we report that pancreatic islet-like clusters derived from hESCs are functionally capable of glucose-responsive insulin secretion as well as therapeutic effects. Pancreatic hormone-expressing endocrine cells (ECs) were differentiated from hESCs using a step-wise protocol...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27730537/construction-of-thymus-organoids-from-decellularized-thymus-scaffolds
#20
Asako Tajima, Isha Pradhan, Xuehui Geng, Massimo Trucco, Yong Fan
One of the hallmarks of modern medicine is the development of therapeutics that can modulate immune responses, especially the adaptive arm of immunity, for disease intervention and prevention. While tremendous progress has been made in the past decades, manipulating the thymus, the primary lymphoid organ responsible for the development and education of T lymphocytes, remains a challenge. One of the major obstacles is the difficulty to reproduce its unique extracellular matrix (ECM) microenvironment that is essential for maintaining the function and survival of thymic epithelial cells (TECs), the predominant population of cells in the thymic stroma...
October 12, 2016: Methods in Molecular Biology
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