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https://www.readbyqxmd.com/read/28442587/combined-aurka-and-h3k9-methyltransferase-targeting-inhibits-cell-growth-by-inducing-mitotic-catastrophe
#1
Angela Mathison, Ann Salmonson, Mckenna Missfeldt, Jennifer Bintz, Monique Williams, Sarah Kossak, Asha Nair, Thiago M de Assuncao, Trace A Christensen, Navtej S Buttar, Juan L Iovanna, Robert Huebert, Gwen Lomberk
The current integrative pathobiological hypothesis states that pancreatic cancer (PDAC) develops and progresses in response to an interaction between known oncogenes and downstream epigenomic regulators. Congruently, this study tests a new combinatorial therapy based on the inhibition of the Aurora kinase A (AURKA) oncogene and one of its targets, the H3K9 methylation-based epigenetic pathway. This therapeutic combination is effective at inhibiting the in vitro growth of PDAC cells both, in monolayer culture systems, and in 3D spheroids and organoids...
April 25, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28436965/a-three-dimensional-model-of-human-lung-development-and-disease-from-pluripotent-stem-cells
#2
Ya-Wen Chen, Sarah Xuelian Huang, Ana Luisa Rodrigues Toste de Carvalho, Siu-Hong Ho, Mohammad Naimul Islam, Stefano Volpi, Luigi D Notarangelo, Michael Ciancanelli, Jean-Laurent Casanova, Jahar Bhattacharya, Alice F Liang, Laura M Palermo, Matteo Porotto, Anne Moscona, Hans-Willem Snoeck
Recapitulation of lung development from human pluripotent stem cells (hPSCs) in three dimensions (3D) would allow deeper insight into human development, as well as the development of innovative strategies for disease modelling, drug discovery and regenerative medicine. We report here the generation from hPSCs of lung bud organoids (LBOs) that contain mesoderm and pulmonary endoderm and develop into branching airway and early alveolar structures after xenotransplantation and in Matrigel 3D culture. Expression analysis and structural features indicated that the branching structures reached the second trimester of human gestation...
April 24, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28416576/pathways-involved-in-formation-of-mammary-organoid-architecture-have-keys-to-understanding-drug-resistance-and-to-discovery-of-druggable-targets
#3
Saori Furuta, Mina J Bissell
Signals from the extracellular matrix (ECM) are received at the cell surface receptor, transmitted to the cytoskeletons, and transferred to the nucleus and chromatin for tissue- and context-specific gene expression. Cells, in return, modulate the cell shape and ECM, allowing for the maintenance of tissue homeostasis as well as for coevolution and adaptation to the environmental signals. We postulated the existence of dynamic and reciprocal interactions between the ECM and the nucleus more than three decades ago, but now these pathways have been proven experimentally thanks to the advances in imaging and cell/molecular biology techniques...
April 17, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28391362/stem-cell-derived-organoids-and-their-application-for-medical-research-and-patient-treatment
#4
REVIEW
Sina Bartfeld, Hans Clevers
3D culture has allowed the initiation and expansion of organ-like structures, called organoids, from either tissue-resident adult stem cells or pluripotent stem cells. Today, organoids can be grown to resemble a wide variety of organs, exhibiting remarkable similarity to their in vivo counterparts. As successful organoid generation is possible from virtually every patient, organoids hold a great promise for medical research and the development of new treatments. They have already found their way into the clinic, enabling personalized medicine in small patient trials...
April 8, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28373686/an-update-on-stem-cell-biology-and-engineering-for-brain-development
#5
C J C Parr, S Yamanaka, H Saito
Two recent technologies, induced-pluripotent stem cells (iPSCs) and direct somatic reprogramming, have shown enormous potential for cell-based therapies against intractable diseases such as those that affect the central nervous system. Already, methods that generate most major cell types of the human brain exist. Whether the cell types are directly reprogrammed from human somatic cells or differentiated from an iPSC intermediate, the overview presented here demonstrates how these protocols vary greatly in their efficiencies, purity and maturation of the resulting cells...
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28373416/on-site-cytology-for-development-of-patient-derived-three-dimensional-organoid-cultures-a-pilot-study
#6
Verena Sailer, Chantal Pauli, Elyze C Merzier, Juan Miguel Mosquera, Himisha Beltran, Mark A Rubin, Rema A Rao
BACKGROUND/AIM: Development of patient-derived three-dimensional (3D) organoid cultures is an emerging technique in the field of precision oncology. We aimed to integrate on-site adequacy evaluation using cytology into the tumor organoid development workflow to ensure precise characterization and growth of these cultures. PATIENTS AND METHODS: Cancer patients were consented to a Precision Medicine trial. Fresh tissue was procured for genomic analyses as well as organoid development...
April 2017: Anticancer Research
https://www.readbyqxmd.com/read/28361479/a-simple-method-of-generating-3d-brain-organoids-using-standard-laboratory-equipment
#7
Magdalena Sutcliffe, Madeline A Lancaster
3D brain organoids are a powerful tool with prospective application for the study of neural development and disease. Here we describe the growth factor-free method of generating cerebral organoids from feeder-dependent or feeder-free human pluripotent stem cells using standard laboratory equipment. The protocol outlined below allows generation of 3D tissues, which replicate human early in vivo brain development up to the end of the first trimester, both in terms of morphology and gene expression pattern.
March 31, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28361321/formation-of-stomach-tissue-by-organoid-culture-using-mouse-embryonic-stem-cells
#8
Taka-Aki K Noguchi, Akira Kurisaki
In this chapter, we describe a method for the induction of stomach organoids from mouse embryonic stem (ES) cells. We used an embryoid body-based differentiation method to induce gastric primordial epithelium covered with mesenchyme and further differentiate it in Matrigel by 3D culture. The differentiated organoid contains both corpus- and antrum-specific mature gastric tissue cells. This protocol may be useful for a variety of studies in developmental biology and disease modeling of the stomach.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28361311/directed-differentiation-of-mouse-embryonic-stem-cells-into-inner-ear-sensory-epithelia-in-3d-culture
#9
Jing Nie, Karl R Koehler, Eri Hashino
The inner ear sensory epithelium harbors mechanosensory hair cells responsible for detecting sound and maintaining balance. This protocol describes a three-dimensional (3D) culture system that efficiently generates inner ear sensory epithelia from aggregates of mouse embryonic stem (mES) cells. By mimicking the activations and repressions of key signaling pathways during in vivo inner ear development, mES cell aggregates are sequentially treated with recombinant proteins and small molecule inhibitors for activating or inhibiting the Bmp, TGFβ, Fgf, and Wnt signaling pathways...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28361309/reconstitution-of-a-patterned-neural-tube-from-single-mouse-embryonic-stem-cells
#10
Keisuke Ishihara, Adrian Ranga, Matthias P Lutolf, Elly M Tanaka, Andrea Meinhardt
The recapitulation of tissue development and patterning in three-dimensional (3D) culture is an important dimension of stem cell research. Here, we describe a 3D culture protocol in which single mouse ES cells embedded in Matrigel under neural induction conditions clonally form a lumen containing, oval-shaped epithelial structure within 3 days. By Day 7 an apicobasally polarized neuroepithelium with uniformly dorsal cell identity forms. Treatment with retinoic acid at Day 2 results in posteriorization and self-organization of dorsal-ventral neural tube patterning...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28341301/disease-modeling-in-stem-cell-derived-3d-organoid-systems
#11
REVIEW
Devanjali Dutta, Inha Heo, Hans Clevers
Organoids are 3D in vitro culture systems derived from self-organizing stem cells. They can recapitulate the in vivo architecture, functionality, and genetic signature of original tissues. Thus, organoid technology has been rapidly applied to understanding stem cell biology, organogenesis, and various human pathologies. The recent development of human patient-derived organoids has enabled disease modeling with precision, highlighting their great potential in biomedical applications, translational medicine, and personalized therapy...
March 21, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28339648/three-dimensional-testicular-organoid-a-novel-tool-for-the-study-of-human-spermatogenesis-and-gonadotoxicity-in-vitro%C3%A2
#12
Samuel S Pendergraft, Hooman Sadri-Ardekani, Anthony Atala, Colin E Bishop
Existing methods for evaluating the potential gonadotoxicity of environmental agents and pharmaceutical compounds rely heavily on animal studies. The current gold standard in vivo functional assays in animals are limited in their human predictive capacity. In addition, existing human two-dimensional in vitro models of testicular toxicity do not accurately reflect the in vivo situation. A more reliable testicular in vitro model system is needed to better assess the gonadotoxic potential of drugs prior to progression into clinical trials...
March 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28333915/directed-differentiation-of-human-induced-pluripotent-stem-cells-into-functional-cholangiocyte-like-cells
#13
Fotios Sampaziotis, Miguel Cardoso de Brito, Imbisaat Geti, Alessandro Bertero, Nicholas Rf Hannan, Ludovic Vallier
The difficulty in isolating and propagating functional primary cholangiocytes is a major limitation in the study of biliary disorders and the testing of novel therapeutic agents. To overcome this problem, we have developed a platform for the differentiation of human pluripotent stem cells (hPSCs) into functional cholangiocyte-like cells (CLCs). We have previously reported that our 26-d protocol closely recapitulates key stages of biliary development, starting with the differentiation of hPSCs into endoderm and subsequently into foregut progenitor (FP) cells, followed by the generation of hepatoblasts (HBs), cholangiocyte progenitors (CPs) expressing early biliary markers and mature CLCs displaying cholangiocyte functionality...
April 2017: Nature Protocols
https://www.readbyqxmd.com/read/28314175/choosing-wisely-preclinical-test-models-in-the-era-of-precision-medicine
#14
REVIEW
Konrad Klinghammer, Wolfgang Walther, Jens Hoffmann
Through the introduction of a steadily growing variety of preclinical test models drug development and biomarker research has advanced. Next to classical used 2D cell line cultures, tissue-slice cultures, 3D organoid cell cultures, genetically engineered mouse models, cell line derived mouse models and patient derived xenografts may be selected for a specific question. All models harbor advantages and disadvantages. This review focuses on the available preclinical test models, novel developments such as humanized mice and discusses for which question a particular model should be employed...
March 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28314117/three-dimensional-cell-cultures-in-drug-discovery-and-development
#15
Ye Fang, Richard M Eglen
The past decades have witnessed significant efforts toward the development of three-dimensional (3D) cell cultures as systems that better mimic in vivo physiology. Today, 3D cell cultures are emerging, not only as a new tool in early drug discovery but also as potential therapeutics to treat disease. In this review, we assess leading 3D cell culture technologies and their impact on drug discovery, including spheroids, organoids, scaffolds, hydrogels, organs-on-chips, and 3D bioprinting. We also discuss the implementation of these technologies in compound identification, screening, and development, ranging from disease modeling to assessment of efficacy and safety profiles...
March 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28303935/multiscale-microenvironmental-perturbation-of-pluripotent-stem-cell-fate-and-self-organization
#16
Yoji Tabata, Matthias P Lutolf
The combination of microfluidics with engineered three-dimensional (3D) matrices can bring new insights into the fate regulation of stem cells and their self-organization into organoids. Although there has been progress in 3D stem cell culturing, most existing in vitro methodologies do not allow for mimicking of the spatiotemporal heterogeneity of stimuli that drive morphogenetic processes in vivo. To address this, we present a perfusion-free microchip concept for the in vitro 3D perturbation of stem cell fate...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28292842/bringing-together-the-organoid-field-from-early-beginnings-to-the-road-ahead
#17
REVIEW
Senthil K Muthuswamy
From October 12-15th, 2016, EMBO∣EMBL held a symposium to bring together those in the scientific community with a shared interest in using three-dimensional (3D) culture methods to study biology, model disease and personalize treatments. The symposium, entitled 'Organoids: modelling organ development and disease in 3D culture', which was organized by Juergen Knoblich, Mina Bissell and Esther Schnapp, was particularly timely as there were otherwise few opportunities for those interested in using 3D culture platforms to interact outside of their organ-specific scientific community...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28287550/forskolin-induced-swelling-in-intestinal-organoids-an-in-vitro-assay-for-assessing-drug-response-in-cystic-fibrosis-patients
#18
Sylvia F Boj, Annelotte M Vonk, Marvin Statia, Jinyi Su, Robert R G Vries, Jeffrey M Beekman, Hans Clevers
Recently-developed cystic fibrosis transmembrane conductance regulator (CFTR)-modulating drugs correct surface expression and/or function of the mutant CFTR channel in subjects with cystic fibrosis (CF). Identification of subjects that may benefit from these drugs is challenging because of the extensive heterogeneity of CFTR mutations, as well as other unknown factors that contribute to individual drug efficacy. Here, we describe a simple and relatively rapid assay for measuring individual CFTR function and response to CFTR modulators in vitro...
February 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28283582/self-organized-developmental-patterning-and-differentiation-in-cerebral-organoids
#19
Magdalena Renner, Madeline A Lancaster, Shan Bian, Heejin Choi, Taeyun Ku, Angela Peer, Kwanghun Chung, Juergen A Knoblich
Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia...
March 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28277923/3d-culture-as-a-clinically-relevant-model-for-personalized-medicine
#20
Eliza Li Shan Fong, Tan Boon Toh, Hanry Yu, Edward Kai-Hua Chow
Advances in understanding many of the fundamental mechanisms of cancer progression have led to the development of molecular targeted therapies. While molecular targeted therapeutics continue to improve the outcome for cancer patients, tumor heterogeneity among patients, as well as intratumoral heterogeneity, limits the efficacy of these drugs to specific patient subtypes, as well as contributes to relapse. Thus, there is a need for a more personalized approach toward drug development and diagnosis that takes into account the diversity of cancer patients, as well as the complex milieu of tumor cells within a single patient...
March 1, 2017: SLAS Technology
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