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stem cell disease modelling

Irina A Tikhonova, Martin W Hoyle, Tristan M Snowsill, Chris Cooper, Joanna L Varley-Campbell, Claudius E Rudin, Ruben E Mujica Mota
The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE's Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company's submission to NICE...
October 17, 2016: PharmacoEconomics
Edwin D Hawkins, Delfim Duarte, Olufolake Akinduro, Reema A Khorshed, Diana Passaro, Malgorzata Nowicka, Lenny Straszkowski, Mark K Scott, Steve Rothery, Nicola Ruivo, Katie Foster, Michaela Waibel, Ricky W Johnstone, Simon J Harrison, David A Westerman, Hang Quach, John Gribben, Mark D Robinson, Louise E Purton, Dominique Bonnet, Cristina Lo Celso
It is widely accepted that complex interactions between cancer cells and their surrounding microenvironment contribute to disease development, chemo-resistance and disease relapse. In light of this observed interdependency, novel therapeutic interventions that target specific cancer stroma cell lineages and their interactions are being sought. Here we studied a mouse model of human T-cell acute lymphoblastic leukaemia (T-ALL) and used intravital microscopy to monitor the progression of disease within the bone marrow at both the tissue-wide and single-cell level over time, from bone marrow seeding to development/selection of chemo-resistance...
October 17, 2016: Nature
Hyun Sook Hong, Dae Yeon Hwang, Ju Hyeong Park, Suna Kim, Eun Jung Seo, Youngsook Son
Intestinal inflammation alters immune responses in the mucosa and destroys colon architecture, leading to serious diseases such as inflammatory bowel disease (IBD). Thus, regulation of inflammation is regarded as the ultimate therapy for intestinal disease. Substance-P (SP) is known to mediate proliferation, migration, and cellular senescence in a variety of cells. SP was found to mobilize stem cells from bone marrow to the site of injury and to suppress inflammatory responses by inducing regulatory T cells (Tregs) and M2 macrophages...
October 14, 2016: Cytokine
Bing-Ying Xie, Ai-Wen Wu
BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease; current research relies on cancer cell lines and animal cancer models, which may not precisely imitate inner human tumors and guide clinical medicine. The purpose of our study was to explore and further improve the process of producing three-dimensional (3D) organoid model and impel the development of personalized therapy. METHODS: We subcutaneously injected surgically resected CRC tissues from a patient into BALB/c-nu mice to build patient-derived xenografts (PDXs)...
2016: Chinese Medical Journal
Ritva Heljasvaara, Mari Aikio, Heli Ruotsalainen, Taina Pihlajaniemi
Collagen XVIII is a ubiquitous basement membrane (BM) proteoglycan produced in three tissue-specific isoforms that differ in their N-terminal non-collagenous sequences, but share collagenous and C-terminal non-collagenous domains. The collagenous domain provides flexibility to the large collagen XVIII molecules on account of multiple interruptions in collagenous sequences. Each isoform has a complex multi-domain structure that endows it with an ability to perform various biological functions. The long isoform contains a frizzled-like (Fz) domain with Wnt-inhibiting activity and a unique domain of unknown function (DUF959), which is also present in the medium isoform...
October 13, 2016: Matrix Biology: Journal of the International Society for Matrix Biology
Natalie Weber, Kristin Schwanke, Stephan Greten, Meike Wendland, Bogdan Iorga, Martin Fischer, Cornelia Geers-Knörr, Jan Hegermann, Christoph Wrede, Jan Fiedler, Henning Kempf, Annika Franke, Birgit Piep, Angelika Pfanne, Thomas Thum, Ulrich Martin, Bernhard Brenner, Robert Zweigerdt, Theresia Kraft
Human pluripotent stem cell (hPSC)-derived cardiomyocytes hold great potential for in vitro modeling of diseases like cardiomyopathies. Yet, knowledge about expression and functional impact of sarcomeric protein isoforms like the myosin heavy chain (MyHC) in hPSC-cardiomyocytes is scarce. We hypothesized that ventricular β-MyHC expression alters contraction and calcium kinetics and drives morphological and electrophysiological differentiation towards ventricular-like cardiomyocytes. To address this, we (1) generated human embryonic stem cell-derived cardiomyocytes (hESC-CMs) that switched towards exclusive β-MyHC, and (2) functionally and morphologically characterized these hESC-CMs at the single-cell level...
November 2016: Basic Research in Cardiology
Jonathan C Niclis, Carlos W Gantner, Walaa F Alsanie, Stuart J McDougall, Chris R Bye, Andrew G Elefanty, Edouard G Stanley, John M Haynes, Colin W Pouton, Lachlan H Thompson, Clare L Parish
: : Recent studies have shown evidence for the functional integration of human pluripotent stem cell (hPSC)-derived ventral midbrain dopamine (vmDA) neurons in animal models of Parkinson's disease. Although these cells present a sustainable alternative to fetal mesencephalic grafts, a number of hurdles require attention prior to clinical translation. These include the persistent use of xenogeneic reagents and challenges associated with scalability and storage of differentiated cells. In this study, we describe the first fully defined feeder- and xenogeneic-free protocol for the generation of vmDA neurons from hPSCs and utilize two novel reporter knock-in lines (LMX1A-eGFP and PITX3-eGFP) for in-depth in vitro and in vivo tracking...
October 14, 2016: Stem Cells Translational Medicine
Naoya Uchida, Juan J Haro-Mora, Atsushi Fujita, Duck-Yeon Lee, Thomas Winkler, Matthew M Hsieh, John F Tisdale
Human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells represent an ideal source for in vitro modeling of erythropoiesis and a potential alternative source for red blood cell transfusions. However, iPS cell-derived erythroid cells predominantly produce ε- and γ-globin without β-globin production. We recently demonstrated that ES cell-derived sacs (ES sacs), known to express hemangioblast markers, allow for efficient erythroid cell generation with β-globin production. In this study, we generated several iPS cell lines derived from bone marrow stromal cells (MSCs) and peripheral blood erythroid progenitors (EPs) from sickle cell disease patients, and evaluated hematopoietic stem/progenitor cell (HSPC) generation after iPS sac induction as well as subsequent erythroid differentiation...
October 14, 2016: Stem Cells
D M Lavin, B E Bintz, C G Thanos
Hydrogel microcapsules have been used for decades to encapsulate cells and treat diseases ranging from neurodegenerative disorders to more systemic applications like Type I Diabetes. This cell encapsulation modality has been developed through more cumulative experiments than perhaps any other, owing to the relative ease of accessing the required materials, the commercial availability of droplet-generating instrumentation, and the mild microenvironment and unique permeability properties of hydrogels that are difficult to attain with alternative encapsulation systems employing thermoplastic materials...
2017: Methods in Molecular Biology
Thangavelu Soundara Rajan, Sabrina Giacoppo, Oriana Trubiani, Francesca Diomede, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon
Conditioned medium derived from mesenchymal stem cells (MSCs) shows immunomodulatory and neuroprotective effects in preclinical models. Given the difficulty to harvest MSCs from bone marrow and adipose tissues, research has been focused to find alternative resources for MSCs, such as oral-derived tissues. Recently, we have demonstrated the protective effects of MSCs obtained from healthy human periodontal ligament tissue (hPDLSCs) in murine experimental autoimmune encephalomyelitis model. In the present in vitro study, we have investigated the immunomodulatory and neuroprotective effects of conditioned medium obtained from hPDLSCs of Relapsing Remitting- Multiple sclerosis (RR-MS) patients on NSC34 mouse motoneurons stimulated with lipopolysaccharide (LPS)...
October 11, 2016: Experimental Cell Research
Jun Fan, Quan Zhou, Zaisheng Qin, Tao Tao
BACKGROUND: Propofol is a widely used intravenous anesthetic that is well-known for its protective effect in various human and animal disease models. However, the effects of propofol on neurogenesis, especially on the development of neural stem cells (NSCs), remains unknown. Related microRNAs may act as important regulators in this process. METHODS: Published Gene Expression Omnibus (GEO) DataSets related to propofol were selected and re-analyzed to screen neural development-related genes and predict microRNA (miRNA) expression using bioinformatic methods...
October 13, 2016: BMC Anesthesiology
Bart Ellenbroek, Jiun Youn
Rodents (especially Mus musculus and Rattus norvegicus) have been the most widely used models in biomedical research for many years. A notable shift has taken place over the last two decades, with mice taking a more and more prominent role in biomedical science compared to rats. This shift was primarily instigated by the availability of a much larger genetic toolbox for mice, particularly embryonic-stem-cell-based targeting technology for gene disruption. With the recent emergence of tools for altering the rat genome, notably genome-editing technologies, the technological gap between the two organisms is closing, and it is becoming more important to consider the physiological, anatomical, biochemical and pharmacological differences between rats and mice when choosing the right model system for a specific biological question...
October 1, 2016: Disease Models & Mechanisms
Hannah L Bader, Tien Hsu
BACKGROUND: Mutations in the tumor suppressor gene von Hippel-Lindau (VHL) underlie a hereditary cancer syndrome-VHL disease-and are also frequently observed in sporadic renal cell carcinoma of the clear cell type (ccRCC). VHL disease is characterized by malignant and benign tumors in a few specific tissues, including ccRCC, hemangioblastoma and pheochromocytoma. The etiology of these tumors remains unresolved. METHODS: Conditional inactivation of the VHL gene in mouse (Vhlh) was generated to examine the pathophysiological role of the VHL gene function...
October 12, 2016: BMC Cancer
Mi-Young Son, Young-Dae Kim, Binna Seol, Mi-Ok Lee, Hee-Jun Na, Bin Yoo, Jae-Suk Chang, Yee Sook Cho
Behçet's disease (BD) is a chronic inflammatory and multisystemic autoimmune disease of unknown etiology. Due to the lack of a specific test for BD, its diagnosis is very difficult, and therapeutic options are limited. Induced pluripotent stem cell (iPSC) technology, which provides inaccessible disease-relevant cell types, opens a new era for disease treatment. Here, we generated BD iPSCs from patient somatic cells and differentiated them into hematopoietic precursor cells (BD iPSC-HPCs) as BD model cells...
October 12, 2016: Stem Cells and Development
Annie C Bowles, Amy L Strong, Rachel M Wise, Robert C Thomas, Brittany Y Gerstein, Maria F Dutreil, Ryan S Hunter, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes...
October 12, 2016: Stem Cells
Domenico Albino, Gianluca Civenni, Simona Rossi, Abhishek Mitra, Carlo V Catapano, Giuseppina M Carbone
Metastatic prostate cancer represents a yet unsolved clinical problem due to the high frequency of relapse and treatment resistance. Understanding the pathways that lead to prostate cancer progression is an important task to prevent this deadly disease. The ETS transcription factor ESE3/EHF has an important role in differentiation of human prostate epithelial cells. Loss of ESE3/EHF in prostate epithelial cells determines transformation, epithelial-to-mesenchymal transition (EMT) and acquisition of stem-like properties...
October 8, 2016: Oncotarget
Eleonora Cianci, Oriana Trubiani, Francesca Diomede, Ilaria Merciaro, Ida Meschini, Pantaleone Bruni, Fausto Croce, Mario Romano
Lipoxin (LX)A4 is a lipoxygenase-formed arachidonic acid metabolite with potent anti-inflammatory, pro-resolution properties. Its therapeutic efficacy has been largely demonstrated in a variety of cellular, preclinical and clinical models. Among these, periodontal disease, where LXA4 promotes tissue repair, also by modulating functions of human periodontal ligament stem cells (hPDLSCs). As medicated biomembranes may be particularly useful in clinical settings, where local stimulation of tissue repair is needed, we used electrospinning to embed LXA4 in membranes made of poly(ethylene oxide) (PEO) and poly(D,L-lactide) (PDLLA)...
October 9, 2016: International Journal of Pharmaceutics
Thomas Westergard, Brigid K Jensen, Xinmei Wen, Jingli Cai, Elizabeth Kropf, Lorraine Iacovitti, Piera Pasinelli, Davide Trotti
Aberrant hexanucleotide repeat expansions in C9orf72 are the most common genetic change underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). RNA transcripts containing these expansions undergo repeat-associated non-ATG translation (RAN-T) to form five dipeptide repeat proteins (DPRs). DPRs are found as aggregates throughout the CNS of C9orf72-ALS/FTD patients, and some cause degeneration when expressed in vitro in neuronal cultures and in vivo in animal models. The spread of characteristic disease-related proteins drives the progression of pathology in many neurodegenerative diseases...
October 11, 2016: Cell Reports
Panos Roussos, Boris Guennewig, Dominik C Kaczorowski, Guy Barry, Kristen J Brennand
Importance: Schizophrenia candidate genes participate in common molecular pathways that are regulated by activity-dependent changes in neurons. One important next step is to further our understanding on the role of activity-dependent changes of gene expression in the etiopathogenesis of schizophrenia. Objective: To examine whether neuronal activity-dependent changes of gene expression are dysregulated in schizophrenia. Design, Setting, and Participants: Neurons differentiated from human-induced pluripotent stem cells derived from 4 individuals with schizophrenia and 4 unaffected control individuals were depolarized using potassium chloride...
October 12, 2016: JAMA Psychiatry
Stefan Thiem, Moritz F Eissmann, Emma Stuart, Joachim Elzer, Anna Jonas, Michael Buchert, Matthias Ernst
Temporal and spatial regulation of genes mediated by tissue-specific promoters and conditional gene expression systems provide a powerful tool to study gene function in health, disease and during development. Although transgenic mice expressing the Cre recombinase in the gastric epithelium have been reported, there is a lack of models that allow inducible and reversible gene modification in the stomach. Here, we exploited the gastrointestinal epithelium-specific expression pattern of the three trefoil factor (Tff) genes and bacterial artificial chromosome transgenesis to generate a novel mouse strain that expresses the CreERT2 recombinase and the reverse tetracycline transactivator (rtTA)...
October 12, 2016: Genesis: the Journal of Genetics and Development
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