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organotypic culture

Olivia Krefft, Ammar Jabali, Vira Iefremova, Philipp Koch, Julia Ladewig
The human cortex is highly expanded and exhibits a complex structure with specific functional areas, providing higher brain function, such as cognition. Efforts to study human cerebral cortex development have been limited by the availability of model systems. Translating results from rodent studies to the human system is restricted by species differences and studies on human primary tissues are hampered by a lack of tissue availability as well as ethical concerns. Recent development in human pluripotent stem cell (PSC) technology include the generation of three-dimensional (3D) self-organizing organotypic culture systems, which mimic to a certain extent human-specific brain development in vitro...
January 23, 2018: Journal of Visualized Experiments: JoVE
Justin M Balko, Jeffrey A Sosman
Immunotherapy has transformed the therapeutic landscape of cancer, but the preclinical evaluation of combination approaches that will deepen and broaden its clinical benefit has lagged far behind due to the lack of expedient and easily accessible ex vivo human systems. In this issue, Jenkins and colleagues and Deng and colleagues report the use of organotypic cultures of tumors derived from mice and humans containing both tumor cells and cells from their local immune microenvironment to recapitulate the in vivo use of immune checkpoint inhibitors and extend the application of this system to therapeutic combinations of immune checkpoint blockade and molecularly targeted agents...
February 2018: Cancer Discovery
Caroline Le Duigou, Etienne Savary, Mélanie Morin-Brureau, Daniel Gomez-Dominguez, André Sobczyk, Farah Chali, Giampaolo Milior, Larissa Kraus, Jochen C Meier, Dimitri M Kullmann, Bertrand Mathon, Liset Menendez de la Prida, Georg Dorfmuller, Johan Pallud, Emmanuel Eugène, Stéphane Clemenceau, Richard Miles
BACKGROUND: Insights into human brain diseases may emerge from tissue obtained after operations on patients. However techniques requiring transduction of transgenes carried by viral vectors cannot be applied to acute human tissue. NEW METHOD: We show that organotypic culture techniques can be used to maintain tissue from patients with three different neurological syndromes for several weeks in vitro. Optimized viral vector techniques and promoters for transgene expression are described...
February 7, 2018: Journal of Neuroscience Methods
Anna Pomerenke
Human lung cancer is one of the leading causes of death worldwide, with nearly 2 million of new cases diagnosed each year, often too late for a successful therapeutic intervention. In this chapter, organotypic models of lung cancer will be reviewed. Ex vivo tissue explants, spheroids, organoids, and novel bioengineering approaches are currently being used to study human lung cancer. Although there is no ideal method that will fully recapitulate the complex human lung architecture, the three-dimensional (3D) organotypic models described here represent a major advance from classical two-dimensional (2D) tissue culture models...
February 9, 2018: Current Topics in Microbiology and Immunology
Pauline De Berdt, Pauline Bottemanne, John Bianco, Mireille Alhouayek, Anibal Diogenes, Amy Llyod, Jose Gerardo-Nava, Gary A Brook, Véronique Miron, Giulio G Muccioli, Anne des Rieux
Secondary damage following spinal cord injury leads to non-reversible lesions and hampering of the reparative process. The local production of pro-inflammatory cytokines such as TNF-α can exacerbate these events. Oligodendrocyte death also occurs, followed by progressive demyelination leading to significant tissue degeneration. Dental stem cells from human apical papilla (SCAP) can be easily obtained at the removal of an adult immature tooth. This offers a minimally invasive approach to re-use this tissue as a source of stem cells, as compared to biopsying neural tissue from a patient with a spinal cord injury...
February 7, 2018: Cellular and Molecular Life Sciences: CMLS
Francis J P Ebling, Jo E Lewis
Studies from a number of areas of neuroendocrinology indicate that hypothalamic tanycytes play a key role in control of energy metabolism. First, profound annual changes in gene expression have been identified in these unusual glial cells in seasonal mammals, for example in genes relating to the transport and metabolism of thyroid hormone into the hypothalamus. The consequent changes in local thyroid hormone availability in the hypothalamus have been shown experimentally to regulate annual cycles in energy intake, storage and expenditure in seasonal species...
February 7, 2018: Glia
S Leverrier-Penna, R T Mitchell, E Becker, L Lecante, M Ben Maamar, N Homer, V Lavoué, D M Kristensen, N Dejucq-Rainsford, B Jégou, S Mazaud-Guittot
STUDY QUESTION: Does ibuprofen use during the first trimester of pregnancy interfere with the development of the human fetal ovary? SUMMARY ANSWER: In human fetuses, ibuprofen exposure is deleterious for ovarian germ cells. WHAT IS KNOWN ALREADY: In utero stages of ovarian development define the future reproductive capacity of a woman. In rodents, analgesics can impair the development of the fetal ovary leading to early onset of fertility failure...
February 2, 2018: Human Reproduction
L Hämäläinen, E Kärkkäinen, P Takabe, L Rauhala, G Bart, R Kärnä, S Pasonen-Seppänen, S Oikari, M I Tammi, R H Tammi
BACKGROUND: Hyaluronan is a large, linear glycosaminoglycan present throughout the narrow extracellular space of the vital epidermis. Increased hyaluronan metabolism takes place in epidermal hypertrophy, wound healing and cancer. Hyaluronan is produced by hyaluronan synthases (HAS1-3) and catabolized by hyaluronidases (HYAL1 and -2), reactive oxygen species (ROS), and the KIAA1199 protein. OBJECTIVES: To investigate the changes in hyaluronan metabolism during epidermal stratification and maturation, and the impact of vitamin C...
February 6, 2018: British Journal of Dermatology
N Sumru Bayin, Lin Ma, Dimitris G Placantonakis, Mary Helen Barcellos-Hoff
Glioblastoma (GBM), a deadly primary brain malignancy, manifests pronounced radioresistance. Identifying agents that improve the sensitivity of tumor tissue to radiotherapy is critical for improving patient outcomes. The response to ionizing radiation is regulated by both cell-intrinsic and -extrinsic mechanisms. In particular, the tumor microenvironment is known to promote radioresistance in GBM. Therefore, model systems used to test radiosensitizing agents need to take into account the tumor microenvironment...
2018: Methods in Molecular Biology
Yan Li, Pengcheng Wang, Chuanlin Hu, Kun Wang, Qing Chang, Lieju Liu, Zhenggang Han, Yang Shao, Ying Zhai, Zhengyu Zuo, Zhiyong Gong, Yang Wu
Exposure to PM2.5 has become one of the most important factors affecting public health in the world. Both clinical and research studies have suggested that PM2.5 inhalation is associated with impaired lung function. In this study, material characterization identified the existence of nanoscale particulate matter (NPM) in airborne PM2.5 samples. When coming into contact with protein-rich fluids, the NPM becomes covered by a protein layer that forms a "protein corona". Based on a 3D organotypic cell culture, the protein corona was shown to mitigate NPM cytotoxicity and further stimulate the proliferation of human lung fibroblasts (HLFs)...
January 31, 2018: Scientific Reports
Silvia Albertini, Irene Lo Cigno, Federica Calati, Marco De Andrea, Cinzia Borgogna, Valentina Dell'Oste, Santo Landolfo, Marisa Gariglio
Although it is clear that high-risk human papillomaviruses (HPVs) can selectively infect keratinocytes and persist in the host, it still remains to be unequivocally determined whether they can escape antiviral innate immunity by interfering with pattern recognition receptor (PRR) signaling. In this study, we have assessed the innate immune response in monolayer and organotypic raft cultures of NIKS cells harboring multiple copies of episomal HPV18 (NIKSmcHPV18), which fully recapitulates the persistent state of infection...
January 31, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Soria Eladak, Delphine Moison, Marie-Justine Guerquin, Gabriele Matilionyte, Karen Kilcoyne, Thierry N'Tumba-Byn, Sébastien Messiaen, Yoann Deceuninck, Stéphanie Pozzi-Gaudin, Alexandra Benachi, Gabriel Livera, Jean-Philippe Antignac, Rod Mitchell, Virginie Rouiller-Fabre, René Habert
BACKGROUND: Using an organotypic culture system termed human Fetal Testis Assay (hFeTA) we previously showed that 0.01 μM BPA decreases basal, but not LH-stimulated, testosterone secreted by the first trimester human fetal testis. The present study was conducted to determine the potential for a long-term antiandrogenic effect of BPA using a xenograft model, and also to study the effect of BPA on germ cell development using both the hFETA and xenograft models. METHODS: Using the hFeTA system, first trimester testes were cultured for 3 days with 0...
2018: PloS One
Mario M Modena, Ketki Chawla, Patrick M Misun, Andreas Hierlemann
Technological advances in microfabrication techniques in combination with organotypic cell and tissue models have enabled the realization of microphysiological systems capable of recapitulating aspects of human physiology in vitro with great fidelity. Concurrently, a number of analysis techniques has been developed to probe and characterize these model systems. However, many assays are still performed off-line, which severely compromises the possibility to obtain real-time information from the samples under examination, and which also limits the use of these platforms in high-throughput analysis...
January 30, 2018: ACS Chemical Biology
Tanja Eisemann, Barbara Costa, Jens Strelau, Michel Mittelbronn, Peter Angel, Heike Peterziel
BACKGROUND: The poor prognosis for glioblastoma patients is caused by the diffuse infiltrative growth pattern of the tumor. Therefore, the molecular and cellular processes underlying cell migration continue to be a major focus of glioblastoma research. Emerging evidence supports the concept that the tumor microenvironment has a profound influence on the functional properties of tumor cells. Accordingly, substantial effort must be devoted to move from traditional two-dimensional migration assays to three-dimensional systems that more faithfully recapitulate the complex in vivo tumor microenvironment...
January 30, 2018: BMC Cancer
Justyna Janowska, Malgorzata Ziemka-Nalecz, Joanna Sypecka
Oligodendrocyte progenitor cells (OPCs) constitute one of the main populations of dividing cells in the central nervous system (CNS). Physiologically, OPCs give rise to mature, myelinating oligodendrocytes and confer trophic support to their neighboring cells within the nervous tissue. OPCs are known to be extremely sensitive to the influence of exogenous clues which might affect their crucial biological processes, like survival, proliferation, differentiation, and the ability to generate a myelin membrane...
January 24, 2018: International Journal of Molecular Sciences
Chris S Pridgeon, Constanze Schlott, Min Wei Wong, Minne B Heringa, Tobias Heckel, Joe Leedale, Laurence Launay, Vitalina Gryshkova, Stefan Przyborski, Rachel N Bearon, Emma L Wilkinson, Tahera Ansari, John Greenman, Delilah F G Hendriks, Sue Gibbs, James Sidaway, Rowena L Sison-Young, Paul Walker, Mike J Cross, B Kevin Park, Chris E P Goldring
The development of improved, innovative models for the detection of toxicity of drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new products safely to market in a cost-effective and timely manner. In addition, improvement in models to detect toxicity may reduce the incidence of unexpected post-marketing toxicity and reduce or eliminate the need for animal testing. The safety of novel products of the pharmaceutical, chemical, or cosmetics industry must be assured; therefore, toxicological properties need to be assessed...
January 23, 2018: Archives of Toxicology
Jessy Cartier, Chinthika Piyasena, Sarah A Sparrow, James P Boardman, Amanda J Drake
Preterm birth affects 5-18% of all babies and is associated with neurodevelopmental impairment and increased neuropsychiatric disease risk. Although preterm birth associates with differential DNA methylation at neurodevelopmental genes in buccal DNA, including Leucine-rich alpha-2-glycoprotein 1 (LRG1), it is not known whether these differences also occur in the brain, or if they persist. Thus, there is a need for animal models or in vitro systems in which to undertake longitudinal and mechanistic studies. We used a combination of in vivo rat studies and ex vivo experiments in rat cortical slices to explore their utility in modelling the human preterm brain...
January 22, 2018: European Journal of Neuroscience
Claire Henry, Neville Hacker, Caroline Ford
OBJECTIVE: Elevated expression of the ROR1 and ROR2 Wnt receptors has been noted in both the tumour and stromal compartments of ovarian cancer patient tissue samples. In vitro studies have suggested these receptors play a role in ovarian cancer metastasis. However, these previous studies have utilised simple 2D in vitro models to investigate cancer cell growth and migration, which does not allow investigation of stromal involvement in Wnt driven metastasis. AIM: To investigate targeting ROR1 and ROR2 using a primary co-culture 3D model of epithelial ovarian cancer dissemination to the omentum...
December 22, 2017: Oncotarget
C Ceresa, G Nicolini, S Semperboni, V Gandin, M Monfrini, F Avezza, P Alberti, A Bravin, M Pellei, C Santini, Guido Cavaletti
[Cu(thp)4]PF6, [Cu(PTA)4]PF6, [Au(thp)4]PF6 and [Au(PTA)4]PF6 are phosphane (thp = tris(hydroxymethyl)phosphane; PTA = 1,3,5-triaza-7-phosphaadamantane) copper(I) and gold(I) water-soluble complexes characterized by high anticancer activity in a wide range of solid tumors, often able to overcome drug resistance of platinum-based compounds. For these reasons, they have been proposed as a valid alternative to platinum-based chemotherapeutic drugs (e.g., cisplatin and oxaliplatin). In vitro experiments performed on organotypic cultures of dorsal root ganglia (DRG) from 15-day-old rat embryos revealed that copper-based compounds were not neurotoxic even at concentrations higher than the IC50 obtained in human cancer cells while [Au(PTA)4]PF6 was neurotoxic at lower concentration than IC50 in cancer cell lines...
January 17, 2018: Neurotoxicity Research
Cayla A Thompson, Ann DeLaForest, Michele A Battle
The gastrointestinal (GI) tract, in simplest terms, can be described as an epithelial-lined muscular tube extending along the cephalocaudal axis from the oral cavity to the anus. Although the general architecture of the GI tract organs is conserved from end to end, the presence of different epithelial tissue structures and unique epithelial cell types within each organ enables each to perform the distinct digestive functions required for efficient nutrient assimilation. Spatiotemporal regulation of signaling pathways and downstream transcription factors controls GI epithelial morphogenesis during development to confer essential regional-specific epithelial structures and functions...
January 12, 2018: Developmental Biology
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