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Madeline Williams, Smrithi Prem, Xiaofeng Zhou, Paul Matteson, Percy Luk Yeung, Chi-Wei Lu, Zhiping Pang, Linda Brzustowicz, James H Millonig, Emanuel Dicicco-Bloom
Human brain development proceeds through a series of precisely orchestrated processes, with earlier stages distinguished by proliferation, migration, and neurite outgrowth; and later stages characterized by axon/dendrite outgrowth and synapse formation. In neurodevelopmental disorders, often one or more of these processes are disrupted, leading to abnormalities in brain formation and function. With the advent of human induced pluripotent stem cell (hiPSC) technology, researchers now have an abundant supply of human cells that can be differentiated into virtually any cell type, including neurons...
March 2, 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
Yuta Kasagi, Prasanna M Chandramouleeswaran, Kelly A Whelan, Koji Tanaka, Veronique Giroux, Medha Sharma, Joshua Wang, Alain J Benitez, Maureen DeMarshall, John W Tobias, Kathryn E Hamilton, Gary W Falk, Jonathan M Spergel, Andres J Klein-Szanto, Anil K Rustgi, Amanda B Muir, Hiroshi Nakagawa
Background & Aims: Aberrations in the esophageal proliferation-differentiation gradient are histologic hallmarks in eosinophilic esophagitis (EoE) and gastroesophageal reflux disease. A reliable protocol to grow 3-dimensional (3D) esophageal organoids is needed to study esophageal epithelial homeostasis under physiological and pathologic conditions. Methods: We modified keratinocyte-serum free medium to grow 3D organoids from endoscopic esophageal biopsies, immortalized human esophageal epithelial cells, and murine esophagi...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Maria Perez-Lanzon, Guido Kroemer, Maria Chiara Maiuri
In less than a decade, organoid systems have emerged as an innovative and valid in vitro method to mimic in vivo pathophysiology. Organoids are 3D structures constituted by multiple organ-specific cell types that self-organize and can function as miniature organs. Organoids have quickly become an important tool for basic and translational research with wide applications for disease modeling, drug screening, drug optimization, and personalized and regenerative medicine. In this review, we summarize the recent utilization of organoids for modeling human genetic diseases, a research area with promising biomedical applications...
2018: International Review of Cell and Molecular Biology
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
Yasmine Baktash, Anisha Madhav, Kelly E Coller, Glenn Randall
Hepatitis C virus (HCV) enters hepatocytes via various entry factors, including scavenger receptor BI (SR-B1), cluster of differentiation 81 (CD81), epidermal growth factor receptor (EGFR), claudin-1 (CLDN1), and occludin (OCLN). As CLDN1 and OCLN are not readily accessible due to their tight junctional localization, HCV likely accesses them by either disrupting cellular polarity or migrating to the tight junction. In this study, we image HCV entry into a three-dimensional polarized hepatoma system and reveal that the virus sequentially engages these entry factors through actin-dependent mechanisms...
March 14, 2018: Cell Host & Microbe
Plansky Hoang, Jason Wang, Bruce R Conklin, Kevin E Healy, Zhen Ma
The creation of human induced pluripotent stem cells (hiPSCs) has provided an unprecedented opportunity to study tissue morphogenesis and organ development through 'organogenesis-in-a-dish'. Current approaches to cardiac organoid engineering rely on either direct cardiac differentiation from embryoid bodies (EBs) or generation of aligned cardiac tissues from predifferentiated cardiomyocytes from monolayer hiPSCs. To experimentally model early cardiac organogenesis in vitro, our protocol combines biomaterials-based cell patterning with stem cell organoid engineering...
April 2018: Nature Protocols
Bárbara da Silva, Ryan K Mathew, Euan S Polson, Jennifer Williams, Heiko Wurdak
Organoid methodology provides a platform for the ex vivo investigation of the cellular and molecular mechanisms underlying brain development and disease. The high-grade brain tumor glioblastoma multiforme (GBM) is considered a cancer of unmet clinical need, in part due to GBM cell infiltration into healthy brain parenchyma, making complete surgical resection improbable. Modeling the process of GBM invasion in real time is challenging as it requires both tumor and neural tissue compartments. Here, we demonstrate that human GBM spheroids possess the ability to spontaneously infiltrate early-stage cerebral organoids (eCOs)...
March 1, 2018: SLAS Discovery
Teklab Gebregiworgis, Christopher Boyd Marshall, Tadateru Nishikawa, Nikolina Radulovich, María-José Sandi, Zhenhao Fang, Robert Rottapel, Ming-Sound Tsao, Mitsuhiko Ikura
Small GTPases (sGTPases) are critical switch-like regulators that mediate several important cellular functions and are often mutated in human cancers. They are activated by guanine nucleotide exchange factors (GEFs), which specifically catalyze the exchange of GTP for GDP. GEFs coordinate signaling networks in normal cells, and are frequently deregulated in cancers. sGTPase signaling pathways are complex and interconnected; however, most GEF assays do not reveal such complexity. In this communication, we describe the development of a unique real-time NMR-based multiplexed GEF assay that employs distinct isotopic labeling schemes for each sGTPase protein to enable simultaneous observation of six proteins of interest...
March 15, 2018: Journal of the American Chemical Society
Leticia Moreira, Basil Bakir, Priya Chatterji, Zahra Dantes, Maximilian Reichert, Anil K Rustgi
Pancreatic ductal adenocarcinoma is one of the most aggressive forms of cancer, and the third leading cause of cancer-related mortality in the United States. Although important advances have been made in the last decade, the mortality rate of pancreatic ductal adenocarcinoma has not changed appreciably. This review summarizes a rapidly emerging model of pancreatic cancer research, focusing on 3-dimensional organoids as a powerful tool for several applications, but above all, representing a step toward personalized medicine...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Takahiro Yoshida, Nikolai A Sopko, Max Kates, Xiaopu Liu, Gregory Joice, David J McConkey, Trinity J Bivalacqua
There has been increasing awareness of the importance of three-dimensional culture of cancer cells. Tumor cells growing as multicellular spheroids in three-dimensional culture, alternatively called organoids, are widely believed to more closely mimic solid tumors in situ . Previous studies concluded that the Wnt/β-catenin pathway is required for regeneration of the normal urothelium after injury and that β-catenin is upregulated in human bladder cancers, but no clear evidence has been advanced to support the idea that the Wnt/β-catenin pathway is directly involved in deregulated proliferation and the other malignant characteristics of bladder cancer cells...
February 16, 2018: Oncotarget
Cindy J M Loomans, Nerys Williams Giuliani, Jeetindra Balak, Femke Ringnalda, Léon van Gurp, Meritxell Huch, Sylvia F Boj, Toshiro Sato, Lennart Kester, Susana M Chuva de Sousa Lopes, Matthias S Roost, Susan Bonner-Weir, Marten A Engelse, Ton J Rabelink, Harry Heimberg, Robert G J Vries, Alexander van Oudenaarden, Françoise Carlotti, Hans Clevers, Eelco J P de Koning
Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi ), express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC), and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue...
March 13, 2018: Stem Cell Reports
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
Seyed Mohammad Hossein Kashfi, Sheema Almozyan, Nicholas Jinks, Bon-Kyoung Koo, Abdolrahman S Nateri
Organoids have extensive applications in many fields ranging from modelling human development and disease, personalised medicine, drug screening, etc. Moreover, in the last few years, several studies have evaluated the capacity of organoids as transplantation sources for therapeutic approaches and regenerative medicine. Nevertheless, depending on the origin of the cells and anatomical complications, an organoid transplant may make tissue regeneration difficult. However, some essential aspects of organoids including the morphological alterations and the growth pattern of the matched tumour and their healthy derived organoids have received less attention...
February 13, 2018: Oncotarget
Andrew Leber, Raquel Hontecillas, Nuria Tubau-Juni, Victoria Zoccoli-Rodriguez, Vida Abedi, Josep Bassaganya-Riera
Interactions among the gut microbiome, dysregulated immune responses, and genetic factors contribute to the pathogenesis of inflammatory bowel disease (IBD). Nlrx1 -/- mice have exacerbated disease severity, colonic lesions, and increased inflammatory markers. Global transcriptomic analyses demonstrate enhanced mucosal antimicrobial defense response, chemokine and cytokine expression, and epithelial cell metabolism in colitic Nlrx1 -/- mice compared to wild-type (WT) mice. Cell-specificity studies using cre-lox mice demonstrate that the loss of NLRX1 in intestinal epithelial cells (IEC) recapitulate the increased sensitivity to DSS colitis observed in whole body Nlrx1 -/- mice...
2018: Frontiers in Immunology
Conor A Bradley
No abstract text is available yet for this article.
March 14, 2018: Nature Reviews. Gastroenterology & Hepatology
Joshua Shepherd
No abstract text is available yet for this article.
March 13, 2018: Journal of Medical Ethics
(no author information available yet)
In a recent study, organoids derived from the metastatic tumors of patients with gastrointestinal cancers had a similar response to treatment as the original tumors. Eventually, organoids could become a useful tool for identifying the most effective therapy for each patient.
March 13, 2018: Cancer Discovery
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
Jonathan Braverman, Ömer H Yilmaz
In this issue of Developmental Cell, Thorne et al. (2018) describe a simple, scalable method to culture 2D enteroid monolayers that surprisingly recapitulates many of the features of 3D organoid cultures and in vivo intestinal tissue and can be used for high-throughput microscopy-based experiments.
March 12, 2018: Developmental Cell
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