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https://www.readbyqxmd.com/read/29774633/a-simple-and-cost-efficient-adherent-culture-platform-for-human-gastric-primary-cells-as-an-in-vitro-model-for-helicobacter-pylori-infection
#1
Samaneh Saberi, Behshad Pournasr, Zahra Farzaneh, Maryam Esmaeili, Mahmoud Eshagh Hosseini, Hossein Baharvand, Marjan Mohammadi
BACKGROUND: Most two- dimensional in vitro models for studying host- H. pylori interactions rely on tumor-derived cell lines, which harbor malignant alterations. The recent development of human gastric organoids has overcome this limitation and provides a highly sophisticated, yet costly, short-term model for H. pylori infection, with restricted use in low-budget centers. METHOD: Tissue specimens from upper, middle, and lower stomachs of H. pylori-negative volunteers were collectively dispersed and cultured on mouse embryonic fibroblast (MEF) or collagen-coated plates...
May 17, 2018: Helicobacter
https://www.readbyqxmd.com/read/29774115/an-improved-method-for-culturing-patient-derived-colorectal-cancer-spheroids
#2
Hiroyuki Miyoshi, Hisatsugu Maekawa, Fumihiko Kakizaki, Tadayoshi Yamaura, Kenji Kawada, Yoshiharu Sakai, M Mark Taketo
Recent advances allowed culturing and examination of patient-derived colorectal cancer (PD-CRC) cells as organoids or spheroids. To be applied to practical personalized medicine, however, current methods still need to be strengthened for higher efficiency. Here we report an improved method to propagate PD-CRC tumor initiating cells (TICs) in spheroid culture. We established > 100 cancer spheroid lines derived from independent colorectal cancer patients employing a serum-containing medium with additional inhibitors, Y27632 and SB431542...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29771306/drug-screening-for-human-genetic-diseases-using-ipsc-models
#3
Matthew S Elitt, Lilianne Barbar, Paul J Tesar
Induced pluripotent stem cells (iPSCs) enable the generation of previously unattainable, scalable quantities of disease-relevant tissues from patients suffering from essentially any genetic disorder. This cellular material has proven instrumental for drug screening efforts on these disorders, and has facilitated the identification of novel therapeutics for patients. Here we will review the foundational technologies that have enabled iPSCs, the power and limitations of iPSC-based compound screens along with screening guidelines, and recent examples of screening efforts...
May 16, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29770526/current-status-of-3-d-organoids-as-pre-clinical-models
#4
REVIEW
Garima Kaushik, Moorthy P Ponnusamy, Surinder K Batra
Three-dimensional (3D) cultures use the property of some cells to self-organize in matrices and generate structures that can be programmed to represent an organ or a pathology. Organoid cultures are the 3D cultivation of source tissue (ranging from cells to tissue fragments) in a support matrix and specialized media that nearly resembles the physiological environment. Depending on the source tissue, growth factors, and inhibitors provided, organoids can be programmed to recapitulate the biology of a system and progression of pathology...
May 17, 2018: Stem Cells
https://www.readbyqxmd.com/read/29769665/bioengineering-strategies-to-accelerate-stem-cell-therapeutics
#5
REVIEW
Christopher M Madl, Sarah C Heilshorn, Helen M Blau
Although only a few stem cell-based therapies are currently available to patients, stem cells hold tremendous regenerative potential, and several exciting clinical applications are on the horizon. Biomaterials with tuneable mechanical and biochemical properties can preserve stem cell function in culture, enhance survival of transplanted cells and guide tissue regeneration. Rapid progress with three-dimensional hydrogel culture platforms provides the opportunity to grow patient-specific organoids, and has led to the discovery of drugs that stimulate endogenous tissue-specific stem cells and enabled screens for drugs to treat disease...
May 2018: Nature
https://www.readbyqxmd.com/read/29760764/human-brain-organoids-on-a-chip-reveal-the-physics-of-folding
#6
Eyal Karzbrun, Aditya Kshirsagar, Sidney R Cohen, Jacob H Hanna, Orly Reiner
Human brain wrinkling has been implicated in neurodevelopmental disorders and yet its origins remain unknown. Polymer gel models suggest that wrinkling emerges spontaneously due to compression forces arising during differential swelling, but these ideas have not been tested in a living system. Here, we report the appearance of surface wrinkles during the in vitro development and self-organization of human brain organoids in a micro-fabricated compartment that supports in situ imaging over a timescale of weeks...
May 2018: Nature Physics
https://www.readbyqxmd.com/read/29760729/ceramic-hollow-fibre-constructs-for-continuous-perfusion-and-cell-harvest-from-3d-hematopoietic-organoids
#7
Mark C Allenby, Asma Tahlawi, José C F Morais, Kang Li, Nicki Panoskaltsis, Athanasios Mantalaris
Tissue vasculature efficiently distributes nutrients, removes metabolites, and possesses selective cellular permeability for tissue growth and function. Engineered tissue models have been limited by small volumes, low cell densities, and invasive cell extraction due to ineffective nutrient diffusion and cell-biomaterial attachment. Herein, we describe the fabrication and testing of ceramic hollow fibre membranes (HFs) able to separate red blood cells (RBCs) and mononuclear cells (MNCs) and be incorporated into 3D tissue models to improve nutrient and metabolite exchange...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29760697/hookworm-secreted-extracellular-vesicles-interact-with-host-cells-and-prevent-inducible-colitis-in-mice
#8
Ramon M Eichenberger, Stephanie Ryan, Linda Jones, Geraldine Buitrago, Ramona Polster, Marcela Montes de Oca, Jennifer Zuvelek, Paul R Giacomin, Lindsay A Dent, Christian R Engwerda, Matthew A Field, Javier Sotillo, Alex Loukas
Gastrointestinal (GI) parasites, hookworms in particular, have evolved to cause minimal harm to their hosts, allowing them to establish chronic infections. This is mediated by creating an immunoregulatory environment. Indeed, hookworms are such potent suppressors of inflammation that they have been used in clinical trials to treat inflammatory bowel diseases (IBD) and celiac disease. Since the recent description of helminths (worms) secreting extracellular vesicles (EVs), exosome-like EVs from different helminths have been characterized and their salient roles in parasite-host interactions have been highlighted...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29760071/prdm1-silences-stem-cell-related-genes-and-inhibits-proliferation-of-human-colon-tumor-organoids
#9
Changlong Liu, Carolyn E Banister, Charles C Weige, Diego Altomare, Joseph H Richardson, Carlo M Contreras, Phillip J Buckhaults
PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated that PRDM1β is a p53-response gene in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. We engineered PRDM1 knockouts and overexpression clones in RKO cells and characterized the PRDM1-dependent transcript landscapes, revealing that both the α and β transcript isoforms repress MYC-response genes and stem cell-related genes...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29756386/kras-mutation-and-epithelial-macrophage-interplay-in-pancreatic-neoplastic-transformation
#10
Faraz Bishehsari, Lijuan Zhang, Usman Barlass, Nailliw Preite, Sanja Turturro, Matthew S Najor, Brandon B Shetuni, Janet P Zayas, Mahboobeh Mahdavinia, Abde M Abukhdeir, Ali Keshavarzian
Pancreatic ductal adenocarcinoma (PDA) is characterized by epithelial mutations in KRAS and prominent tumor-associated inflammation, including macrophage infiltration. But knowledge of early interactions between neoplastic epithelium and macrophages in PDA carcinogenesis is limited. Using a pancreatic organoid model, we found that the expression of mutant KRAS in organoids increased i) ductal to acinar gene expression ratios, ii) epithelial cells proliferation, and iii) colony formation capacity in vitro, and endowed pancreatic cells with the ability to generate neoplastic tumors in vivo...
May 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29756208/impact-of-loss-of-function-mutations-at-the-rnf43-locus-on-colorectal-cancer-development-and-progression
#11
Tsugio Eto, Keisuke Miyake, Katsuhiko Nosho, Masaki Ohmuraya, Yu Imamura, Kota Arima, Shinichi Kanno, Lingfeng Fu, Yuki Kiyozumi, Daisuke Izumi, Hidetaka Sugihara, Yukiharu Hiyoshi, Yuji Miyamoto, Hiroshi Sawayama, Masaaki Iwatsuki, Yoshifumi Baba, Naoya Yoshida, Toru Furukawa, Kimi Araki, Hideo Baba, Takatsugu Ishimoto
RNF43 mutations are frequently detected in colorectal cancer cells and lead to a loss of function of the ubiquitin E3 ligase. Here, we investigated the clinical significance of RNF43 mutations in a large Japanese cohort and the role of RNF43 at various stages of colorectal cancer development and progression. Mutation analysis of the RNF43 gene locus using pyrosequencing technology detected RNF43 hotspot mutations in 1 (0.88%) of 113 colorectal polyp cases and 30 (6.45%) of 465 colorectal cancer cases. Moreover, patients with colorectal cancer harboring mutated RNF43 experienced a higher recurrence rate than those harboring non-mutated RNF43...
May 13, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29755963/environmental-toxin-screening-using-human-derived-3d-bioengineered-liver-and-cardiac-organoids
#12
Steven D Forsythe, Mahesh Devarasetty, Thomas Shupe, Colin Bishop, Anthony Atala, Shay Soker, Aleksander Skardal
Introduction: Environmental toxins, such as lead and other heavy metals, pesticides, and other compounds, represent a significant health concern within the USA and around the world. Even in the twenty-first century, a plethora of cities and towns in the U.S. have suffered from exposures to lead in drinking water or other heavy metals in food or the earth, while there is a high possibility of further places to suffer such exposures in the near future. Methods: We employed bioengineered 3D human liver and cardiac organoids to screen a panel of environmental toxins (lead, mercury, thallium, and glyphosate), and charted the response of the organoids to these compounds...
2018: Frontiers in Public Health
https://www.readbyqxmd.com/read/29754563/new-synthetic-3d-culture-systems-to-unlock-the-future-of-organoids-in-research-and-therapy
#13
Colin Sanctuary
No abstract text is available yet for this article.
September 2017: Personalized Medicine
https://www.readbyqxmd.com/read/29752411/differential-activities-and-mechanisms-of-the-four-r-spondins-in-potentiating-wnt-%C3%AE-catenin-signaling
#14
Soohyun Park, Jie Cui, Wangsheng A Yu, Ling Wu, Kendra Carmon, Qingyun J Liu
The four R-spondins (RSPO1-4) strongly potentiate Wnt signaling and play critical roles in normal development, adult stem cell survival, and cancer development and aggressiveness. All four RSPOs have been suggested to potentiate Wnt signaling by binding to three related receptors, i.e., leucine-rich repeat containing, G protein-coupled receptors 4, 5 and 6 (LGR4/5/6), and then inducing the clearance of two E3 ubiquitin ligases (RNF43 and ZNRF3) that otherwise would ubiquitinate Wnt receptors for degradation...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29752282/niche-mediated-bmp-smad-signaling-regulates-lung-alveolar-stem-cell-proliferation-and-differentiation
#15
Mei-I Chung, Melissa Bujnis, Christina E Barkauskas, Yoshihiko Kobayashi, Brigid L M Hogan
The bone morphogenetic protein (BMP) signaling pathway, including antagonists, functions in lung development and regeneration of tracheal epithelium from basal stem cells. Here, we explore its role in the alveolar region, where type 2 epithelial cells (AT2s) and Pdgfrα+ type 2-associated stromal cells (TASCs) are components of the stem cell niche. We use organoids and in vivo alveolar regrowth after pneumonectomy (PNX) - a process that requires proliferation of AT2s and differentiation into type 1 cells (AT1s)...
May 11, 2018: Development
https://www.readbyqxmd.com/read/29751274/engineering-mesenchymal-stem-cell-spheroids-by-incorporation-of-mechanoregulator-microparticles
#16
Fatemeh Abbasi, Mohammad Hossein Ghanian, Hossein Baharvand, Bahman Vahidi, Mohamadreza Baghaban Eslaminejad
Mechanical forces throughout human mesenchymal stem cell (hMSC) spheroids (mesenspheres) play a predominant role in determining cellular functions of cell growth, proliferation, and differentiation through mechanotransductional mechanisms. Here, we introduce microparticle (MP) incorporation as a mechanical intervention method to alter tensional homeostasis of the mesensphere and explore MSC differentiation in response to MP stiffness. The microparticulate mechanoregulators with different elastic modulus (34 kPa, 0...
May 3, 2018: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/29749250/development-and-characterization-of-human-cerebral-organoids-an-optimized-protocol
#17
Abraam M Yakoub, Mark Sadek
Studies of human neurodevelopmental disorders and stem cell-based regenerative transplants have been hampered by the lack of a model of the developing human brain. Stem cell-derived neurons suffer major limitations, including the ability to recapitulate the 3-dimensional architecture of a brain tissue and the representation of multiple layers and cell types that contribute to the overall brain functions in vivo. Recently, cerebral organoid technology was introduced; however, such technology is still in its infancy, and its low reproducibility and limitations significantly reduce the reliability of such a model as it currently exists, especially considering the complexity of cerebral-organoid protocols...
January 1, 2018: Cell Transplantation
https://www.readbyqxmd.com/read/29748516/journey-into-bone-models-a-review
#18
REVIEW
Julia Scheinpflug, Moritz Pfeiffenberger, Alexandra Damerau, Franziska Schwarz, Martin Textor, Annemarie Lang, Frank Schulze
Bone is a complex tissue with a variety of functions, such as providing mechanical stability for locomotion, protection of the inner organs, mineral homeostasis and haematopoiesis. To fulfil these diverse roles in the human body, bone consists of a multitude of different cells and an extracellular matrix that is mechanically stable, yet flexible at the same time. Unlike most tissues, bone is under constant renewal facilitated by a coordinated interaction of bone-forming and bone-resorbing cells. It is thus challenging to recreate bone in its complexity in vitro and most current models rather focus on certain aspects of bone biology that are of relevance for the research question addressed...
May 10, 2018: Genes
https://www.readbyqxmd.com/read/29748327/vascularizing-the-kidney-in-the-embryo-and-organoid-questioning-assumptions-about-renal-vasculogenesis
#19
David A D Munro, Jamie A Davies
No abstract text is available yet for this article.
May 10, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29748182/a-pdx-organoid-biobank-of-advanced-prostate-cancers-captures-genomic-and-phenotypic-heterogeneity-for-disease-modeling-and-therapeutic-screening
#20
Michael L Beshiri, Caitlin M Tice, Crystal Tran, Holly M Nguyen, Adam G Sowalsky, Supreet Agarwal, Keith H Jansson, Qi Yang, Kerry A McGowen, Juan Juan Yin, Aian Neil Alilin, Fatima H Karzai, William Dahut, Eva Corey, Kathleen Kelly
PURPOSE: Prostate cancer translational research has been hampered by the lack of comprehensive and tractable models   that represent the genomic landscape of clinical disease. Metastatic castrate-resistant prostate cancer (mCRPC) patient-derived xenografts (PDXs) recapitulate the genetic and phenotypic diversity of the disease. We sought to establish a representative, preclinical platform of PDX-derived organoids that is experimentally facile for high throughput and mechanistic analysis...
May 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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