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https://www.readbyqxmd.com/read/29328793/novel-molecular-and-phenotypic-insights-into-congenital-lung-malformations
#1
Daniel T Swarr, William H Peranteau, Jennifer Pogoriler, David B Frank, N Scott Adzick, Holly L Hedrick, Mike Morley, Su Zhou, Edward E Morrisey
RATIONALE: Disruption of normal pulmonary development is a leading cause of morbidity and mortality in infants. Congenital lung malformations are a unique model to study the molecular pathogenesis of isolated structural birth defects as they are often surgically resected. OBJECTIVES: To provide insight into the molecular pathogenesis of congenital lung malformations through analysis of cell-type and gene expression changes in these lesions. METHODS: Clinical data, and lung tissue for DNA, RNA, and histology were obtained from 58 infants undergoing surgical resection of a congenital lung lesion...
January 12, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29321049/human-liver-organoids-generated-with-single-donor-derived-multiple-cells-rescue-mice-from-acute-liver-failure
#2
Yun-Zhong Nie, Yun-Wen Zheng, Miyuki Ogawa, Etsuko Miyagi, Hideki Taniguchi
BACKGROUND: Acute liver failure (ALF) is a life-threatening disease with a high mortality rate. However, there are limited treatments or devices available for ALF therapy. Here, we aimed to develop a new strategy for ALF treatment by transplanting functional liver organoids (LOs) generated from single donor-derived human induced pluripotent stem cell (hiPSC) endoderm, endothelial cells (ECs), and mesenchymal cells (MCs). METHODS: First, we isolated ECs and MCs from a single donor umbilical cord (UC) through enzyme digestion and characterized the UC-ECs and UC-MCs by flow cytometry...
January 10, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29317608/epigenetics-and-cerebral-organoids-promising-directions-in-autism-spectrum-disorders
#3
REVIEW
Sheena Louise Forsberg, Mirolyuba Ilieva, Tanja Maria Michel
Autism spectrum disorders (ASD) affect 1 in 68 children in the US according to the Centers for Disease Control and Prevention (CDC). It is characterized by impairments in social interactions and communication, restrictive and repetitive patterns of behaviors, and interests. Owing to disease complexity, only a limited number of treatment options are available mainly for children that alleviate but do not cure the debilitating symptoms. Studies confirm a genetic link, but environmental factors, such as medications, toxins, and maternal infection during pregnancy, as well as birth complications also play a role...
January 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29304256/dynamics-ultrastructure-and-gene-expression-of-human-in-vitro-organized-testis-cells-from-testicular-sperm-extraction-biopsies
#4
Kathrein von Kopylow, Wolfgang Schulze, Andrea Salzbrunn, Matthias Schaks, Elke Schäfer, Beate Roth, Stefan Schlatt, Andrej-Nikolai Spiess
STUDY QUESTION: Is it possible to induce in-vitro reorganization of primary human testis cells from testicular sperm extraction (TESE) biopsies, maintain their long-term cultivation in a 2D system and identify cellular compositions? SUMMARY ANSWER: In-vitro reorganization of primary human testis cells from TESE biopsies and their long-term cultivation on uncoated cell culture dishes is feasible and the cellular compositions can be uncovered through gene expression and microscopic analyses...
January 3, 2018: Molecular Human Reproduction
https://www.readbyqxmd.com/read/29303405/focal-adhesion-kinase-a-potential-therapeutic-target-for-pancreatic-cancer-and-malignant-pleural-mesothelioma
#5
Rajani Kanteti, Tamara Mirzapoiazova, Jacob J Riehm, Immanuel Dhanasingh, Bolot Mambetsariev, Jiale Wang, Prakash Kulkarni, Garima Kaushik, Parthasarathy Seshacharyulu, Moorthy P Ponnusamy, Hedy L Kindler, Mohd W Nasser, Surinder K Batra, Ravi Salgia
The non-receptor cytoplasmic tyrosine kinase, Focal Adhesion Kinase (FAK) is known to play a key role in a variety of normal and cancer cellular functions such as survival, proliferation, migration and invasion. It is highly active and overexpressed in various cancers including Pancreatic Ductal Adenocarcinoma (PDAC) and Malignant Pleural Mesothelioma (MPM). Here, initially, we demonstrate that FAK is overexpressed in both PDAC and MPM cell lines. Then we analyze effects of two small molecule inhibitors PF-573228, and PF-431396, which are dual specificity inhibitors of FAK and proline rich tyrosine kinase 2 (PYK2), as well as VS-6063, another small molecule inhibitor that specifically inhibits FAK but not PYK2 for cell growth, motility and invasion of PDAC and MPM cell lines...
January 5, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29303193/nanoparticle-binding-attenuates-the-pathobiology-of-gastric-cancer-associated-helicobacter-pylori
#6
Dana Westmeier, Gernot Posselt, Angelina Hahlbrock, Sina Bartfeld, Cecilia Vallet, Carmen Abfalter, Dominic Docter, Shirley K Knauer, Silja Wessler, Roland H Stauber
Enteric bacteria may cause severe diseases, including gastric cancer-associated Helicobacter pylori. Their infection paths overlap with the oro-gastrointestinal uptake route for nanoparticles, increasingly occurring during environmental or consumer/medical exposure. By comprehensive independent analytical methods, such as live cell fluorescence, electron as well as atomic force microscopy and elemental analysis, we show that a wide array of nanoparticles (NPs) but not microparticles form complexes with H. pylori and enteric pathogens without the need for specific functionalization...
January 5, 2018: Nanoscale
https://www.readbyqxmd.com/read/29300391/use-of-a-three-layer-gradient-system-of-cells-for-rat-testicular-organoid-generation
#7
João Pedro Alves-Lopes, Olle Söder, Jan-Bernd Stukenborg
We have recently developed a 3D culture system that allows the reorganization of rat primary testicular cells into organoids with a functional blood-testis barrier, as well as the establishment and maintenance of germ cells. The innovative aspect of our model, the three-layer gradient system (3-LGS), comprises cells combined with Matrigel placed between two layers of Matrigel without cells, which creates a gradient of cells and allows the reorganization of testicular cells into organized structures after 5-7 d in culture...
February 2018: Nature Protocols
https://www.readbyqxmd.com/read/29298425/hair-follicle-development-in-mouse-pluripotent-stem-cell-derived-skin-organoids
#8
Jiyoon Lee, Robert Bӧscke, Pei-Ciao Tang, Byron H Hartman, Stefan Heller, Karl R Koehler
The mammalian hair follicle arises during embryonic development from coordinated interactions between the epidermis and dermis. It is currently unclear how to recapitulate hair follicle induction in pluripotent stem cell cultures for use in basic research studies or in vitro drug testing. To date, generation of hair follicles in vitro has only been possible using primary cells isolated from embryonic skin, cultured alone or in a co-culture with stem cell-derived cells, combined with in vivo transplantation...
January 2, 2018: Cell Reports
https://www.readbyqxmd.com/read/29298292/imaging-organoids-a-bright-future-ahead
#9
Anne C Rios, Hans Clevers
Organogenesis, tissue homeostasis and organ function involve complex spatial cellular organization and tissue dynamics. The underlying mechanisms of these processes, and how they are disrupted in disease, are challenging to address in vivo and ethically impossible to study in human. Organoids, three-dimensional (3D) stem cell cultures that self-organize into ex vivo 'mini-organs', now open a new window onto cellular processes within tissue. Light microscopy is a powerful approach to probe the cellular complexity that can be modeled with organoids...
January 3, 2018: Nature Methods
https://www.readbyqxmd.com/read/29289879/regeneration-of-complex-oral-organs-using-3d-cell-organization-technology
#10
REVIEW
Masamitsu Oshima, Miho Ogawa, Takashi Tsuji
The development of organoid techniques for regenerative therapy has progressed remarkably with the use of tissue-derived stem cells and pluripotent stem cells based on stem cell biology and tissue engineering technology. To realize whole-organ replacement therapy as next-generation regenerative medicine, it is expected that fully functional bioengineered organs can be reconstructed using an in vitro three-dimensional (3D) bioengineered organ germ and organoids by stem cell manipulation and self-organization...
December 28, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29286492/streamlined-3d-cerebellar-differentiation-protocol-with-optional-2d-modification
#11
Dwayne B Holmes, Vivi M Heine
Reducing the complexity and cost of differentiation protocols is important for researchers. This interest fits with concerns about possible unintended effects that extrinsic patterning factors might introduce into human pluripotent stem cell (hPSC) models of brain development or pathophysiology, such as masking disease phenotype. Here, we present two cerebellar differentiation protocols for hPSCs, designed with simpler startup method, fewer patterning factors, and less material requirements than previous protocols...
December 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29286482/real-time-measurement-of-epithelial-barrier-permeability-in-human-intestinal-organoids
#12
David R Hill, Sha Huang, Yu-Hwai Tsai, Jason R Spence, Vincent B Young
Advances in 3D culture of intestinal tissues obtained through biopsy or generated from pluripotent stem cells via directed differentiation, have resulted in sophisticated in vitro models of the intestinal mucosa. Leveraging these emerging model systems will require adaptation of tools and techniques developed for 2D culture systems and animals. Here, we describe a technique for measuring epithelial barrier permeability in human intestinal organoids in real-time. This is accomplished by microinjection of fluorescently-labeled dextran and imaging on an inverted microscope fitted with epifluorescent filters...
December 18, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29286416/immuno-fluorescent-labeling-of-microtubules-and-centrosomal-proteins-in-ex-vivo-intestinal-tissue-and-3d-in-vitro-intestinal-organoids
#13
Deborah A Goldspink, Zoe J Matthews, Elizabeth K Lund, Tom Wileman, Mette M Mogensen
The advent of 3D in vitro organoids that mimic the in vivo tissue architecture and morphogenesis has greatly advanced the ability to study key biological questions in cell and developmental biology. In addition, organoids together with recent technical advances in gene editing and viral gene delivery promises to advance medical research and development of new drugs for treatment of diseases. Organoids grown in vitro in basement matrix provide powerful model systems for studying the behavior and function of various proteins and are well suited for live-imaging of fluorescent-tagged proteins...
December 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29286377/the-organoid-reconstitution-assay-ora-for-the-functional-analysis-of-intestinal-stem-and-niche-cells
#14
Matthias Schewe, Andrea Sacchetti, Mark Schmitt, Riccardo Fodde
The intestinal epithelium is characterized by an extremely rapid turnover rate. In mammals, the entire epithelial lining is renewed within 4 - 5 days. Adult intestinal stem cells reside at the bottom of the crypts of Lieberkühn, are earmarked by expression of the Lgr5 gene, and preserve homeostasis through their characteristic high proliferative rate1. Throughout the small intestine, Lgr5+ stem cells are intermingled with specialized secretory cells called Paneth cells. Paneth cells secrete antibacterial compounds (i...
November 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29281008/testicular-organoids-a-new-model-to-study-the-testicular-microenvironment-in-vitro
#15
João Pedro Alves-Lopes, Jan-Bernd Stukenborg
BACKGROUND: In recent decades, a broad range of strategies have been applied to model the testicular microenvironment in vitro. These models have been utilized to study testicular physiology and development. However, a system that allows investigations into testicular organogenesis and its impact in the spermatogonial stem-cell (SSC) niche in vitro has not been developed yet. Recently, the creation of tissue-specific organ-like structures called organoids has resurged, helping researchers to answer scientific questions that previous in vitro models could not help to elucidate...
December 21, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/29276469/using-3d-organoid-cultures-to-model-intestinal-physiology-and-colorectal-cancer
#16
Sarah P Short, Patricia W Costacurta, Christopher S Williams
The three-dimensional (3D) structure of the intestine is a key determinant of differentiation and function; thus, preserving this architecture is an important consideration for studies of intestinal homeostasis and disease. Over the past decade, a number of systems for 3D intestinal organoid cultures have been developed and adapted to model a wide variety of biological phenomenon. Purpose of this review: We discuss the current state of intestinal and colorectal cancer (CRC) 3D modeling, the most common methods for generating organoid cultures, and how these have yielded insights into intestinal physiology and tumor biology...
June 2017: Current Colorectal Cancer Reports
https://www.readbyqxmd.com/read/29275226/reverse-engineering-organogenesis-through-feedback-loops-between-model-systems
#17
REVIEW
Cody Narciso, Jeremiah Zartman
Biological complexity and ethical limitations necessitate models of human development. Traditionally, genetic model systems have provided inexpensive routes to define mechanisms governing organ development. Recent progress has led to 3D human organoid models of development and disease. However, robust methods to control the size and morphology of organoids for high throughput studies need to be developed. Additionally, insights from multiple developmental contexts are required to reveal conserved genes and processes regulating organ growth and development...
December 21, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29274337/generation-of-three-dimensional-retinal-organoids-expressing-rhodopsin-and-s-and-m-cone-opsins-from-mouse-stem-cells
#18
Kaori Ueda, Akishi Onishi, Shin-Ichiro Ito, Makoto Nakamura, Masayo Takahashi
PURPOSE: Three-dimensional retinal organoids can be differentiated from embryonic stem cells/induced pluripotent stem cells (ES/iPS cells) under defined medium conditions. We modified the serum-free floating culture of embryoid body-like aggregates with quick reaggregation (SFEBq) culture procedure to obtain retinal organoids expressing more rod photoreceptors and S- and M-cone opsins. METHODS: Retinal organoids differentiated from mouse Nrl-eGFP iPS cells were cultured in various mediums during photoreceptor development...
December 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29247536/three-dimensional-liver-derived-extracellular-matrix-hydrogel-promotes-liver-organoids-function
#19
Mona Saheli, Mohammadmajid Sepantafar, Behshad Pournasr, Zahra Farzaneh, Massoud Vosough, Abbas Piryaei, Hossein Baharvand
An important advantage of employing extracellular matrix (ECM)-derived biomaterials in tissue engineering is the ability to tailor the biochemical and physical microenvironment of the cells. This study aims to assess whether three-dimensional (3D) liver-derived ECM hydrogel (LEMgel) promotes physiological function of liver organoids generated by self-organization of human hepatocarcinoma cells together with human mesenchymal and endothelial cells. We have optimized the decellularization method to fabricate liver ECM derived from sheep to preserve the greatest content of glycosaminoglycans, collagen, laminin and fibronectin in produced LEMgel...
December 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29238585/human-intestinal-epithelium-in-a-dish-current-models-for-research-into-gastrointestinal-pathophysiology
#20
REVIEW
Manuel Noben, Wiebe Vanhove, Kaline Arnauts, Anabela Santo Ramalho, Gert Van Assche, Séverine Vermeire, Catherine Verfaillie, Marc Ferrante
Determining the exact pathogenesis of chronic gastrointestinal diseases remains difficult due to the complex in vivo environment. In this review we give an overview of the available epithelial cell culture systems developed to investigate pathophysiology of gastrointestinal diseases. Traditionally used two-dimensional (2D) immortalised (tumour) cell lines survive long-term, but are not genetically stable nor represent any human in particular. In contrast, primary cultures are patient unique, but short-lived...
December 2017: United European Gastroenterology Journal
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