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https://www.readbyqxmd.com/read/27923051/electrophysiological-characteristics-of-human-ipsc-derived-cardiomyocytes-for-the-assessment-of-drug-induced-proarrhythmic-potential
#1
Wataru Yamamoto, Keiichi Asakura, Hiroyuki Ando, Tomohiko Taniguchi, Atsuko Ojima, Takaaki Uda, Tomoharu Osada, Seiji Hayashi, Chieko Kasai, Norimasa Miyamoto, Hiroyuki Tashibu, Takashi Yoshinaga, Daiju Yamazaki, Atsushi Sugiyama, Yasunari Kanda, Kohei Sawada, Yuko Sekino
The aims of this study were to (1) characterize basic electrophysiological elements of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that correspond to clinical properties such as QT-RR relationship, (2) determine the applicability of QT correction and analysis methods, and (3) determine if and how these in-vitro parameters could be used in risk assessment for adverse drug-induced effects such as Torsades de pointes (TdP). Field potential recordings were obtained from commercially available hiPSC-CMs using multi-electrode array (MEA) platform with and without ion channel antagonists in the recording solution...
2016: PloS One
https://www.readbyqxmd.com/read/27923030/patient-derived-induced-pluripotent-stem-cells-in-cancer-research-and-precision-oncology
#2
Eirini P Papapetrou
Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how the method intersects with other patient-derived models of cancer, such as organoids, organs-on-chips and patient-derived xenografts (PDXs). We highlight the opportunities that iPSC models can provide beyond those offered by existing systems and animal models and present current challenges and crucial areas for future improvements toward wider adoption of this technology...
December 6, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27922848/lung-regeneration-steps-toward-clinical-implementation-and-use
#3
Elizabeth A Calle, Katherine L Leiby, MichaSam B Raredon, Laura E Niklason
PURPOSE OF REVIEW: Whole lung tissue engineering is a relatively new area of investigation. In a short time, however, the field has advanced quickly beyond proof of concept studies in rodents and now stands on the cusp of wide-spread scale up to large animal studies. Therefore, this technology is ever closer to being directly clinically relevant. RECENT FINDINGS: The main themes in the literature include refinement of the fundamental components of whole lung engineering and increasing effort to direct induced pluripotent stem cells and lung progenitor cells toward use in lung regeneration...
December 5, 2016: Current Opinion in Anaesthesiology
https://www.readbyqxmd.com/read/27922138/mitomycin-c-treated-human-induced-pluripotent-stem-cells-as-a-safe-delivery-system-of-gold-nanorods-for-targeted-photothermal-therapy-of-gastric-cancer
#4
Meng Yang, Yanlei Liu, Wenxiu Hou, Xiao Zhi, Chunlei Zhang, Xinquan Jiang, Fei Pan, Yuming Yang, Jian Ni, Daxiang Cui
Human-induced pluripotent stem cells (iPS) possess an intrinsic tumor tropism ability. However, iPS cells are impeded in clinical applications of tumor therapy due to the formation of teratomas and their survival in normal organs such as the liver, lungs, spleen and kidneys. Mitomycin C (MMC) can overcome this limitation by suppressing iPS proliferation. Herein, we fabricated a safe delivery system of iPS cells treated with MMC loading with gold nanorods (AuNRs) for the targeted photothermal treatment of gastric cancer...
December 6, 2016: Nanoscale
https://www.readbyqxmd.com/read/27921262/a-new-era-of-disease-modeling-and-drug-discovery-using-induced-pluripotent-stem-cells
#5
REVIEW
Wonhee Suh
In 2006, Shinya Yamanaka first reported that in vitro reprogramming of somatic cells toward pluripotency was achieved by simple induction of specific transcription factors. Induced pluripotent stem cell (iPSC) technology has since revolutionized the ways in which we explore the mechanisms of human diseases and develop therapeutics. Here, I describe the recent advances in human iPSC-based disease modeling and drug discovery and discuss the current challenges. Additionally, I outline potential future applications of human iPSCs in classifying patients based on their response to drugs in clinical trials and elucidating optimal patient-specific therapeutic strategies, which will contribute to reduced attrition rates and the development of precision medicine...
December 5, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27921030/describing-the-stem-cell-potency-the-various-methods-of-functional-assessment-and-in-silico-diagnostics
#6
REVIEW
Vimal K Singh, Abhishek Saini, Manisha Kalsan, Neeraj Kumar, Ramesh Chandra
Stem cells are defined by their capabilities to self-renew and give rise to various types of differentiated cells depending on their potency. They are classified as pluripotent, multipotent, and unipotent as demonstrated through their potential to generate the variety of cell lineages. While pluripotent stem cells may give rise to all types of cells in an organism, Multipotent and Unipotent stem cells remain restricted to the particular tissue or lineages. The potency of these stem cells can be defined by using a number of functional assays along with the evaluation of various molecular markers...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27920633/lesch-nyhan-syndrome-models-theories-and-therapies
#7
REVIEW
Scott Bell, Ilaria Kolobova, Liam Crapper, Carl Ernst
Lesch-Nyhan syndrome (LNS) is a rare X-linked disorder caused by mutations in HPRT1, an important enzyme in the purine salvage pathway. Symptoms of LNS include dystonia, gout, intellectual disability, and self-mutilation. Despite having been characterized over 50 years ago, it remains unclear precisely how deficits in hypoxanthine and guanine recycling can lead to such a profound neurological phenotype. Several studies have proposed different hypotheses regarding the etiology of this disease, and several treatments have been tried in patients, though none have led to a satisfactory explanation of the disease...
November 2016: Molecular Syndromology
https://www.readbyqxmd.com/read/27920532/the-effect-of-magnetic-nanoparticles-on-neuronal-differentiation-of-induced-pluripotent-stem-cell-derived-neural-precursors
#8
Klára Jiráková, Monika Šeneklová, Daniel Jirák, Karolína Turnovcová, Magda Vosmanská, Michal Babič, Daniel Horák, Pavel Veverka, Pavla Jendelová
INTRODUCTION: Magnetic resonance (MR) imaging is suitable for noninvasive long-term tracking. We labeled human induced pluripotent stem cell-derived neural precursors (iPSC-NPs) with two types of iron-based nanoparticles, silica-coated cobalt zinc ferrite nanoparticles (CZF) and poly-l-lysine-coated iron oxide superparamagnetic nanoparticles (PLL-coated γ-Fe2O3) and studied their effect on proliferation and neuronal differentiation. MATERIALS AND METHODS: We investigated the effect of these two contrast agents on neural precursor cell proliferation and differentiation capability...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27920151/lin28-is-induced-in-primed-embryonic-stem-cells-and-regulates-let-7-independent-events
#9
Silvia Parisi, Fabiana Passaro, Luigi Russo, Anna Musto, Angelica Navarra, Simona Romano, Giuseppe Petrosino, Tommaso Russo
Lin28 RNA-binding proteins play important roles in pluripotent stem cells, but the regulation of their expression and the mechanisms underlying their functions are still not definitively understood. Here we address the above-mentioned issues in the first steps of mouse embryonic stem cell (ESC) differentiation. We observed that the expression of Lin28 genes is transiently induced soon after the exit of ESCs from the naive ground state and that this induction is due to the Hmga2-dependent engagement of Otx2 with enhancers present at both Lin28 gene loci...
December 5, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27920086/a-role-for-mitotic-bookmarking-of-sox2-in-pluripotency-and-differentiation
#10
Cédric Deluz, Elias T Friman, Daniel Strebinger, Alexander Benke, Mahé Raccaud, Andrea Callegari, Marion Leleu, Suliana Manley, David M Suter
Mitotic bookmarking transcription factors remain bound to chromosomes during mitosis and were proposed to regulate phenotypic maintenance of stem and progenitor cells at the mitosis-to-G1 (M-G1) transition. However, mitotic bookmarking remains largely unexplored in most stem cell types, and its functional relevance for cell fate decisions remains unclear. Here we screened for mitotic chromosome binding within the pluripotency network of embryonic stem (ES) cells and show that SOX2 and OCT4 remain bound to mitotic chromatin through their respective DNA-binding domains...
December 5, 2016: Genes & Development
https://www.readbyqxmd.com/read/27919783/the-potential-of-induced-pluripotent-stem-cells-as-a-tool-to-study-skeletal-dysplasias-and-cartilage-related-pathologic-conditions
#11
REVIEW
Huan Liu, Lei Yang, Fang Fang Yu, Sen Wang, Cuiyan Wu, Chengjuan Qu, Xiong Guo, Mikko J Lammi
The development of induced pluripotent stem cells (iPSCs) technology has opened up new horizons for development of new research tools especially for skeletal dysplasias, which often lack human disease models. Regenerative medicine and tissue engineering could be the next areas to benefit from refinement of iPSC methods to repair focal cartilage defects, while applications for osteoarthritis (OA) and drug screening have evolved rather slowly. Although the advances in iPSC research of skeletal dysplasias and repair of focal cartilage lesions are not directly relevant to OA, they can be considered to pave the way to future prospects and solutions to OA research, too...
December 2, 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27919263/derivation-of-chicken-induced-pluripotent-stem-cells-tolerant-to-newcastle-disease-virus-induced-lysis-through-multiple-rounds-of-infection
#12
Leonardo Susta, Ying He, Jessica M Hutcheson, Yangqing Lu, Franklin D West, Steven L Stice, Ping Yu, Zaid Abdo, Claudio L Afonso
BACKGROUND: Newcastle disease (ND), caused by Newcastle disease virus (NDV), is a devastating disease of poultry and wild birds. ND is prevented by rigorous biocontainment and vaccination. One potential approach to prevent spread of the virus is production of birds that show innate resistance to NDV-caused disease. Induced pluripotent stem cell (iPSC) technology allows adult cells to be reprogrammed into an embryonic stem cell-like state capable of contributing to live offspring and passing on unique traits in a number of species...
December 5, 2016: Virology Journal
https://www.readbyqxmd.com/read/27918727/the-current-state-of-reproductive-biology-research-in-australia-and-new-zealand-core-themes-from-the-society-for-reproductive-biology-annual-meeting-2016
#13
L K Akison, P H Andraweera, M J Bertoldo, H M Brown, J S M Cuffe, T Fullston, O Holland, J E Schjenken
Because reproduction is essential for all life, it is central to our understanding of all aspects of biology. The Society for Reproductive Biology (SRB) 2016 conference held on the Gold Coast (Qld, Australia) displayed the current breadth of reproductive research in Australia and New Zealand, with additional insights from world leaders in the field. This conference review provides a focused summary of the key questions, emerging ideas and novel technologies that were presented in the symposia. Presented research demonstrated key advances in how stem cell biology may allow us to better understand pluripotency, as well as how environmental and lifestyle factors, such as circadian disruption, smoking, alcohol and diet, affect gametogenesis, embryo implantation, placental function and reproductive capacity...
December 6, 2016: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/27918544/a-balance-between-elongation-and-trimming-regulates-telomere-stability-in-stem-cells
#14
Teresa Rivera, Candy Haggblom, Sandro Cosconati, Jan Karlseder
Telomere length maintenance ensures self-renewal of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs); however, the mechanisms governing telomere length homeostasis in these cell types are unclear. Here, we report that telomere length is determined by the balance between telomere elongation, which is mediated by telomerase, and telomere trimming, which is controlled by XRCC3 and Nbs1, homologous recombination proteins that generate single-stranded C-rich telomeric DNA and double-stranded telomeric circular DNA (T-circles), respectively...
December 5, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27918060/effect-of-small-molecules-on-cell-reprogramming
#15
REVIEW
M Baranek, A Belter, M Z Naskręt-Barciszewska, M Stobiecki, W T Markiewicz, J Barciszewski
The essential idea of regenerative medicine is to fix or replace tissues or organs with alive and patient-specific implants. Pluripotent stem cells are able to indefinitely self-renew and differentiate into all cell types of the body which makes them a potent substantial player in regenerative medicine. The easily accessible source of induced pluripotent stem cells may allow obtaining and cultivating tissues in vitro. Reprogramming refers to regression of mature cells to its initial pluripotent state. One of the approaches affecting pluripotency is the usage of low molecular mass compounds that can modulate enzymes and receptors leading to the formation of pluripotent stem cells (iPSCs)...
December 5, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27917881/distinct-and-shared-determinants-of-cardiomyocyte-contractility-in-multi-lineage-competent-ethnically-diverse-human-ipscs
#16
Martin L Tomov, Zachary T Olmsted, Haluk Dogan, Eda Gongorurler, Maria Tsompana, Hasan H Otu, Michael Buck, Eun-Ah Chang, Jose Cibelli, Janet L Paluh
The realization of personalized medicine through human induced pluripotent stem cell (iPSC) technology can be advanced by transcriptomics, epigenomics, and bioinformatics that inform on genetic pathways directing tissue development and function. When possible, population diversity should be included in new studies as resources become available. Previously we derived replicate iPSC lines of African American, Hispanic-Latino and Asian self-designated ethnically diverse (ED) origins with normal karyotype, verified teratoma formation, pluripotency biomarkers, and tri-lineage in vitro commitment...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27917685/phosphodiesterase-10-inhibitors-in-clinical-development-for-cns-disorders
#17
Hugo Geerts, Athan Spiros, Patrick Roberts
Phosphodiesterase 10 inhibitors (PDE10-I), are conceptually attractive drugs with a potential great therapeutic window as their enriched striatal localization may likely stimulate D1R and reduce D2R downstream effects. However, so far selective PDE10-I with efficacy in animal models have not shown benefit in clinical trials and unexpectedly revealed a substantial dyskinesia motor side-effect. Areas covered: This paper reviews the underlying biological rationale of PDE10 as a target in schizophrenia, Parkinson's and Huntington's disease based on peer-reviewed published articles, the status of the different PDE10-I in clinical development for various CNS indications and explores possible reasons for the clinical trial failures and translational disconnect...
December 3, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27917311/rock-inhibition-promotes-attachment-proliferation-and-wound-closure-in-human-embryonic-stem-cell-derived-retinal-pigmented-epithelium
#18
Roxanne H Croze, William J Thi, Dennis O Clegg
PURPOSE: Nonexudative (dry) age-related macular degeneration (AMD), a leading cause of blindness in the elderly, is associated with the loss of retinal pigmented epithelium (RPE) cells and the development of geographic atrophy, which are areas devoid of RPE cells and photoreceptors. One possible treatment option would be to stimulate RPE attachment and proliferation to replace dying/dysfunctional RPE and bring about wound repair. Clinical trials are underway testing injections of RPE cells derived from pluripotent stem cells to determine their safety and efficacy in treating AMD...
November 2016: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/27916777/modeling-inherited-arrhythmia-disorders-using-induced-pluripotent-stem-cell-derived-cardiomyocytes
#19
Vassilios J Bezzerides, Donghui Zhang, William T Pu
Inherited arrhythmia disorders (IADs) are a group of potentially lethal diseases that remain diagnostic and management challenges. Although the genetic basis for many of these disorders is well known, the pathogenicity of individual mutations and the resulting clinical outcomes are difficult to predict. Treatment options remain imperfect, and optimizing therapy for individual patients can be difficult. Recent advances in the derivation of induced pluripotent stem cells (iPSCs) from patients and creation of genetically engineered human models using CRISPR/Cas9 has the potential to dramatically advance translational arrhythmia research...
December 3, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27916601/gaucher-disease-circa-2016-progress-and-ongoing-challenges
#20
REVIEW
Pramod K Mistry, Grisel Lopez, Raphael Schiffmann, Norman W Barton, Neal J Weinreb, Ellen Sidransky
Over the past decades, tremendous progress has been made in the field of Gaucher disease, the inherited deficiency of the lysosomal enzyme glucocerebrosidase. Many of the colossal achievements took place during the course of the sixty-year tenure of Dr. Roscoe Brady at the National Institutes of Health. These include the recognition of the enzymatic defect involved, the isolation and characterization of the protein, the localization and characterization of the gene and its nearby pseudogene, as well as the identification of the first mutant alleles in patients...
November 17, 2016: Molecular Genetics and Metabolism
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