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stem cell disease modelling

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https://www.readbyqxmd.com/read/28335032/allele-specific-ablation-rescues-electrophysiological-abnormalities-in-a-human-ips-cell-model-of-long-qt-syndrome-with-a-calm2-mutation
#1
Yuta Yamamoto, Takeru Makiyama, Takeshi Harita, Kenichi Sasaki, Yimin Wuriyanghai, Mamoru Hayano, Suguru Nishiuchi, Hirohiko Kohjitani, Sayako Hirose, Jiarong Chen, Fumika Yokoi, Taisuke Ishikawa, Seiko Ohno, Kazuhisa Chonabayashi, Hideki Motomura, Yoshinori Yoshida, Minoru Horie, Naomasa Makita, Takeshi Kimura
Background: Calmodulin is a ubiquitous Ca 2+ sensor molecule encoded by three distinct calmodulin genes, CALM1-3 . Recently, mutations in CALM1-3 have been reported to be associated with severe early-onset long-QT syndrome (LQTS). However, the underlying mechanism through which heterozygous calmodulin mutations lead to severe LQTS remains unknown, particularly in human cardiomyocytes. Objectives: We aimed to establish an LQTS disease model associated with a CALM2 mutation (LQT15) using human induced pluripotent stem cells (hiPSCs) and to assess mutant allele-specific ablation by genome editing for the treatment of LQT15...
March 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334324/understanding-the-genetic-landscape-of-small-cell-carcinoma-of-the-urinary-bladder-and-implications-for-diagnosis-prognosis-and-treatment-a-review
#2
Erik J Kouba, Liang Cheng
Importance: Small cell carcinoma of the urinary bladder is a rare and aggressive neuroendocrine tumor of the urinary bladder. Although research has been performed since the first case was reported in 1981, most of our understanding of the disease treatments has been extrapolated from small cell carcinoma of the lung. However, current data on patient survival have been stagnant. Observations: With the advent of advanced molecular diagnostic methods, a new potential for understanding the origin and treatment of small cell carcinoma of the urinary bladder has become evident...
March 23, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28333915/directed-differentiation-of-human-induced-pluripotent-stem-cells-into-functional-cholangiocyte-like-cells
#3
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/28333144/aberrant-ipsc-derived-human-astrocytes-in-alzheimer-s-disease
#4
V C Jones, R Atkinson-Dell, A Verkhratsky, L Mohamet
The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs)...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28332151/blockade-of-neuroglobin-reduces-protection-of-conditioned-medium-from-human-mesenchymal-stem-cells-in-human-astrocyte-model-t98g-under-a-scratch-assay
#5
Eliana Baez-Jurado, Gina Guio Vega, Gjumrakch Aliev, Vadim V Tarasov, Paula Esquinas, Valentina Echeverria, George E Barreto
Previous studies have indicated that paracrine factors (conditioned medium) increase wound closure and reduce reactive oxygen species in a traumatic brain injury in vitro model. Although the beneficial effects of conditioned medium from human adipose tissue-derived mesenchymal stem cells (hMSCA-CM) have been previously suggested for various neurological diseases, their actions on astrocytic cells are not well understood. In this study, we have explored the effect of hMSCA-CM on human astrocyte model (T98G cells) subjected to scratch assay...
March 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28330607/association-between-anti-thymocyte-globulin-exposure-and-survival-outcomes-in-adult-unrelated-haemopoietic-cell-transplantation-a-multicentre-retrospective-pharmacodynamic-cohort-analysis
#6
Rick Admiraal, Stefan Nierkens, Moniek A de Witte, Eefke J Petersen, Ger-Jan Fleurke, Luka Verrest, Svetlana V Belitser, Robbert G M Bredius, Reinier A P Raymakers, Catherijne A J Knibbe, Monique C Minnema, Charlotte van Kesteren, Jurgen Kuball, Jaap J Boelens
BACKGROUND: Anti-thymocyte globulin (ATG) is used to prevent graft-versus-host disease (GvHD) after allogeneic haemopoietic cell transplantation (HCT). However, ATG can also cause delayed immune reconstitution of T cells, negatively affecting survival. We studied the relation between exposure to ATG and clinical outcomes in adult patients with acute leukaemia and myelodysplastic syndrome. METHODS: We did a retrospective, pharmacokinetic-pharmacodynamic analysis of data from patients with acute lymphoid leukaemia, acute myeloid leukaemia, or myelodysplastic syndrome receiving their first T-cell repleted allogeneic peripheral blood stem cell HCT with ATG (thymoglobulin) as part of non-myeloablative conditioning from March 1, 2004, to June 1, 2015...
March 16, 2017: Lancet Haematology
https://www.readbyqxmd.com/read/28329361/sex-hormones-affect-outcome-in-arrhythmogenic-right-ventricular-cardiomyopathy-dysplasia-from-a-stem-cell-derived-cardiomyocyte-based-model-to-clinical-biomarkers-of-disease-outcome
#7
Deniz Akdis, Ardan M Saguner, Khooshbu Shah, Chuanyu Wei, Argelia Medeiros-Domingo, Arnold von Eckardstein, Thomas F Lüscher, Corinna Brunckhorst, H S Vincent Chen, Firat Duru
Aims: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D. Methods and results: The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male)...
February 18, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28328168/intrastriatal-transplantation-of-human-neural-stem-cells-restores-the-impaired-subventricular-zone-in-parkinsonian-mice
#8
Fuxing Zuo, Feng Xiong, Xia Wang, Xueyuan Li, Renzhi Wang, Wei Ge, Xinjie Bao
Cell replacement therapy using neural stem cells (NSCs) transplantation has recently emerged as a promising method of Parkinson's disease (PD) treatment; however, the underlying mechanisms are not fully understood. To gain new insights into the mechanisms of 6-hydroxydopamine (6-OHDA)-induced lesioning and therapeutic efficacy of human NSCs (hNSCs) transplantation, the striatum (ST) of intrastriatal 6-OHDA-injected parkinsonian mice were unilaterally engrafted with undifferentiated hNSCs. A high-throughput quantitative proteomic approach was used to characterize the proteome profiles of PD-related brain regions such as the SN, ST, olfactory bulb (OB), and subventricular zone (SVZ) in these mice...
March 22, 2017: Stem Cells
https://www.readbyqxmd.com/read/28328017/dental-pulp-stem-cells-promote-regeneration-of-damaged-neuron-cells-on-the-cellular-model-of-alzheimer-s-disease
#9
Feixiang Wang, Yali Jia, Jiajing Liu, Jinglei Zhai, Ning Cao, Wen Yue, Huixia He, Xuetao Pei
Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment...
March 22, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28327958/risk-factors-and-a-prognostic-score-for-survival-after-autologous-stem-cell-transplantation-for-relapsed-or-refractory-hodgkin-lymphoma
#10
P J Bröckelmann, H Müller, O Casasnovas, M Hutchings, B von Tresckow, M Jürgens, S J McCall, F Morschhauser, M Fuchs, P Borchmann, C H Moskowitz, A Engert
BACKGROUND: Novel agents are changing the treatment of relapsed or refractory Hodgkin lymphoma (HL). Nevertheless, high-dose chemotherapy and autologous stem-cell transplantation (ASCT) are considered standard of care in eligible patients. To identify patients who could benefit most from novel therapeutic approaches, we investigated a comprehensive set of risk factors for survival after ASCT. METHODS: In this multinational prognostic multivariable modeling study, 23 potential risk factors (RF) were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional hazards regression analyses (part I)...
March 8, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327905/phase-ii-study-of-idelalisib-a-selective-inhibitor-of-pi3k%C3%AE-for-relapsed-refractory-classical-hodgkin-lymphoma
#11
A K Gopal, M A Fanale, C H Moskowitz, A R Shustov, S Mitra, W Ye, A Younes, A J Moskowitz
Background: The phosphatidylinositol-3-kinase delta (PI3Kδ) inhibitor idelalisib has been shown to block downstream intracellular signaling, reduce the production of prosurvival chemokines and induce apoptosis in classical Hodgkin lymphoma (HL) cell lines. It has also been shown to inhibit regulatory T cells and myeloid-derived suppressor cells in other tumor models. We hypothesized that inhibiting PI3Kδ would have both direct and indirect antitumor effects by directly targeting the malignant cells as well as modulating the inflammatory microenvironment...
January 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28327192/dna-double-strand-breaks-in-human-induced-pluripotent-stem-cell-reprogramming-and-long-term-in-vitro-culturing
#12
Pavel Simara, Lenka Tesarova, Daniela Rehakova, Pavel Matula, Stanislav Stejskal, Ales Hampl, Irena Koutna
BACKGROUND: Human induced pluripotent stem cells (hiPSCs) play roles in both disease modelling and regenerative medicine. It is critical that the genomic integrity of the cells remains intact and that the DNA repair systems are fully functional. In this article, we focused on the detection of DNA double-strand breaks (DSBs) by phosphorylated histone H2AX (known as γH2AX) and p53-binding protein 1 (53BP1) in three distinct lines of hiPSCs, their source cells, and one line of human embryonic stem cells (hESCs)...
March 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28326803/when-is-an-alveolar-type-2-cell-an-alveolar-type-2-cell-a-conundrum-for-lung-stem-cell-biology-and-regenerative-medicine
#13
Michael F Beers, Yuben Moodley
Generating mature, differentiated, adult lung cells from pluripotent cells such as induced pluripotent cells (iPS) and embryonic stem cells (ES) offers the hope of both generating disease specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung regenerative medicine, several groups have developed and reported on protocols utilizing either defined media, co-culture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors...
March 22, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28325755/loss-of-pink1-leads-to-metabolic-deficits-in-adult-neural-stem-cells-and-impedes-differentiation-of-newborn-neurons-in-the-mouse-hippocampus
#14
Sandeep Kumar Agnihotri, Ruifang Shen, Jihong Li, Xu Gao, Hansruedi Büeler
Emerging evidence suggests that mitochondrial dynamics regulates adult hippocampal neurogenesis (AHN). Although abnormal AHN has been linked to depression, anxiety, and cognitive dysfunction, which are features of neurodegenerative conditions, including Parkinson's disease (PD), the impact of mitochondrial deficits on AHN have not been explored previously in a model of neurodegeneration. Here, we used PTEN-induced kinase 1-deficient (PINK1(-/-) ) mice that lacked a mitochondrial kinase mutated in recessive familial PD...
March 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28324469/stem-cells-in-cardiovascular-medicine-the-road-to-regenerative-therapies
#15
REVIEW
Christopher W Anderson, Nicole Boardman, Jiesi Luo, Jinkyu Park, Yibing Qyang
PURPOSE OF REVIEW: The purpose of this review is to provide a broad overview of current trends in stem cell research and its applications in cardiovascular medicine. Researches on different stem cell sources, their inherent characteristics, and the limitations they have in medical applications are discussed. Additionally, uses of stem cells for both modeling and treating cardiovascular disease are discussed, taking note of the obstacles these engineered interventions must overcome to be clinically viable...
April 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28322920/stem-cell-transplantation-therapy-for-multifaceted-therapeutic-benefits-after-stroke
#16
REVIEW
Ling Wei, Zheng Z Wei, Michael Qize Jiang, Osama Mohamad, Shan Ping Yu
One of the exciting advances in modern medicine and life science is cell-based neurovascular regeneration of damaged brain tissues and repair of neuronal structures. The progress in stem cell biology and creation of adult induced pluripotent stem (iPS) cells has significantly improved basic and pre-clinical research in disease mechanisms and generated enthusiasm for potential applications in the treatment of central nervous system (CNS) diseases including stroke. Endogenous neural stem cells and cultured stem cells are capable of self-renewal and give rise to virtually all types of cells essential for the makeup of neuronal structures...
March 16, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28322279/pluripotent-stem-cells-in-neuropsychiatric-disorders
#17
REVIEW
M A Soliman, F Aboharb, N Zeltner, L Studer
Neuropsychiatric disorders place an enormous medical burden on patients across all social and economic ranks. The current understanding of the molecular and cellular causes of neuropsychiatric disease remains limited, which leads to a lack of targeted therapies. Human-induced pluripotent stem cell (iPSC) technology offers a novel platform for modeling the genetic contribution to mental disorders and yields access to patient-specific cells for drug discovery and personalized medicine. Here, we review recent progress in using iPSC technology to model and potentially treat neuropsychiatric disorders by focusing on the most prevalent conditions in psychiatry, including depression, anxiety disorders, bipolar disorder and schizophrenia...
March 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28321424/cell-based-meniscus-repair-and-regeneration-at-the-brink-of-clinical-translation-a-systematic-review-of-preclinical-studies
#18
Jasmijn V Korpershoek, Tommy S de Windt, Michella H Hagmeijer, Lucienne A Vonk, Daniel B F Saris
BACKGROUND: Meniscus damage can be caused by trauma or degeneration and is therefore common among patients of all ages. Repair or regeneration of the menisci could be of great importance not only for pain relief or regaining function but also to prevent degenerative disease and osteoarthritis. Current treatment does not offer consistent long-term improvement. Although preclinical research focusing on augmentation of meniscal tear repair and regeneration after meniscectomy is encouraging, clinical translation remains difficult...
February 2017: Orthopaedic Journal of Sports Medicine
https://www.readbyqxmd.com/read/28321120/decision-analysis-of-allogeneic-hematopoietic-stem-cell-transplantation-for-patients-with-myelodysplastic-syndrome-stratified-according-to-the-revised-international-prognostic-scoring-system-ipss-r
#19
M G Della Porta, C H Jackson, E P Alessandrino, M Rossi, A Bacigalupo, M T van Lint, M Bernardi, B Allione, A Bosi, S Guidi, V Santini, L Malcovati, M Ubezio, C Milanesi, E Todisco, M T Voso, P Musto, F Onida, A P Iori, R Cerretti, G Grillo, A Molteni, P Pioltelli, L Borin, E Angelucci, E Oldani, S Sica, C Pascutto, V Ferretti, A Santoro, F Bonifazi, M Cazzola, A Rambaldi
Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R)...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28320483/human-and-feline-adipose-derived-mesenchymal-stem-cells-have-comparable-phenotype-immunomodulatory-functions-and-transcriptome
#20
Kaitlin C Clark, Fernando A Fierro, Emily Mills Ko, Naomi J Walker, Boaz Arzi, Clifford G Tepper, Heather Dahlenburg, Andrew Cicchetto, Amir Kol, Lyndsey Marsh, William J Murphy, Nasim Fazel, Dori L Borjesson
BACKGROUND: Adipose-derived mesenchymal stem cells (ASCs) are a promising cell therapy to treat inflammatory and immune-mediated diseases. Development of appropriate pre-clinical animal models is critical to determine safety and attain early efficacy data for the most promising therapeutic candidates. Naturally occurring diseases in cats already serve as valuable models to inform human clinical trials in oncologic, cardiovascular, and genetic diseases. The objective of this study was to complete a comprehensive side-by-side comparison of human and feline ASCs, with an emphasis on their immunomodulatory capacity and transcriptome...
March 20, 2017: Stem Cell Research & Therapy
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