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https://www.readbyqxmd.com/read/27931510/generation-of-equine-induced-pluripotent-stem-cells-and-analysis-of-their-therapeutic-potential-for-muscle-injuries
#1
Eun-Mi Lee, Ah-Young Kim, Eun-Joo Lee, Jin-Kyu Park, Se-Il Park, Ssang-Goo Cho, Hong Kyun Kim, Shin-Yoon Kim, Kyu-Shik Jeong
Horse health has become a major concern with the expansion of horse-related industries and sports; the importance of healthy muscles for horse performance and daily activities is undisputed. Here we generated equine-induced pluripotent stem cells (E-iPSCs) by reprogramming equine adipose-derived stem cells (E-ADSCs) into iPSCs using a polycistronic lentiviral vector encoding four transcription factors (i.e., Oct4, Sox2, Klf4, and c-Myc) and then examined their pluripotent characteristics. Subsequently, established E-iPSCs were transplanted into muscle-injured Rag/mdx mice...
November 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27930666/development-of-pet-imaging-to-visualize-activated-macrophages-accumulated-in-the-transplanted-ipsc-derived-cardiac-myocytes-of-allogeneic-origin-for-detecting-the-immune-rejection-of-allogeneic-cell-transplants-in-mice
#2
Noriyuki Kashiyama, Shigeru Miyagawa, Satsuki Fukushima, Takuji Kawamura, Ai Kawamura, Shohei Yoshida, Akima Harada, Tadashi Watabe, Yasukazu Kanai, Koichi Toda, Jun Hatazawa, Yoshiki Sawa
Allogeneic transplantation (Tx) of induced pluripotent stem cells (iPSCs) is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET) imaging targets translocator protein (TSPO), which is highly expressed on mitochondrial membrane, especially in activated macrophage...
2016: PloS One
https://www.readbyqxmd.com/read/27929521/efficient-footprint-free-human-ipsc-genome-editing-by-consolidation-of-cas9-crispr-and-piggybac-technologies
#3
Gang Wang, Luhan Yang, Dennis Grishin, Xavier Rios, Lillian Y Ye, Yong Hu, Kai Li, Donghui Zhang, George M Church, William T Pu
Genome editing of human induced pluripotent stem cells (hiPSCs) offers unprecedented opportunities for in vitro disease modeling and personalized cell replacement therapy. The introduction of Cas9-directed genome editing has expanded adoption of this approach. However, marker-free genome editing using standard protocols remains inefficient, yielding desired targeted alleles at a rate of ∼1-5%. We developed a protocol based on a doxycycline-inducible Cas9 transgene carried on a piggyBac transposon to enable robust and highly efficient Cas9-directed genome editing, so that a parental line can be expeditiously engineered to harbor many separate mutations...
January 2017: Nature Protocols
https://www.readbyqxmd.com/read/27926491/early-pathogenic-event-of-alzheimer-s-disease-documented-in-ipscs-from-patients-with-psen1-mutations
#4
Juan Yang, Hanzhi Zhao, Yu Ma, Guilai Shi, Jian Song, Yu Tang, Song Li, Ting Li, Nan Liu, Fan Tang, Junjie Gu, Lingling Zhang, Zhuohua Zhang, Xiaohui Zhang, Ying Jin, Weidong Le
Alzheimer's disease (AD) is the most common age-related dementia characterized by progressive neuronal loss. However, the molecular mechanisms for the neuronal loss is still debated. Here, we used induced pluripotent stem cells (iPSCs) derived from somatic cells of familial AD patients carrying PSEN1 mutations to study the early pathogenic event of AD. We found that premature neuronal differentiation with decreased proliferation and increased apoptosis occured in AD-iPSC-derived neural progenitor cells (AD-NPCs) once neuronal differentiation was initiated, together with higher levels of Aβ42 and phosphorylated tau...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27925205/generation-of-insulin-producing-cells-from-human-induced-pluripotent-stem-cells-using-a-stepwise-differentiation-protocol-optimized-with-platelet-rich-plasma
#5
Seyed Ehsan Enderami, Yousef Mortazavi, Masoud Soleimani, Samad Nadri, Alireza Biglari, Reyhaneh Nassiri Mansour
Studies on patient-specific human-induced pluripotent stem cells (hiPSCs) as well as a series of autologous growth factors presumably will reveal their many benefits for cell base replacement therapy in type 1 diabetes mellitus (TIDM) patients in the future. For this purpose, we established a multistep protocol by adding platelet-rich plasma (PRP) that induce the hiPSCs into insulin-producing cells (IPCs). We present here a differentiation protocol consisting of five stages in two groups including protocol with PRP and without PRP...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924875/gabab-receptor-mediates-opposing-adaptations-of-gaba-release-from-two-types-of-prefrontal-interneurons-after-observational-fear
#6
Lei Liu, Wataru Ito, Alexei Morozov
The observational fear (OF) paradigm in rodents, in which the subject is exposed to a distressed conspecific, elicits contextual fear learning and enhances future passive avoidance learning, which may model certain behavioral traits resulting from traumatic experiences in humans. Because these behaviors affected by the OF, require dorso-medial prefrontal cortex (dmPFC), we searched for synaptic adaptations in dmPFC resulting from OF in mice by recording synaptic responses in dmPFC layer V pyramidal neurons elicited by repeated 5 Hz electrical stimulation of dmPFC layer I, or by optogenetic stimulation of specific interneurons ex vivo one day after OF...
December 7, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27923633/diversity-of-glycosphingolipid-gm2-and-cholesterol-accumulation-in-npc1-patient-specific-ipsc-derived-neurons
#7
Michaela Trilck, Franziska Peter, Chaonan Zheng, Marcus Frank, Kostantin Dobrenis, Hermann Mascher, Arndt Rolfs, Moritz J Frech
Niemann-Pick disease Type C1 (NPC1) is a rare progressive neurodegenerative disorder caused by mutations in the NPC1 gene. On the cellular level NPC1 mutations lead to an accumulation of cholesterol and gangliosides. As a thorough analysis of the severely affected neuronal cells is unfeasible in NPC1 patients, we recently described the cellular phenotype of neuronal cells derived from NPC1 patient iPSCs carrying the compound heterozygous mutation c.1836A>C/c.1628delC. Here we expanded the analysis to cell lines carrying the prevalent mutation c...
December 3, 2016: Brain Research
https://www.readbyqxmd.com/read/27923051/electrophysiological-characteristics-of-human-ipsc-derived-cardiomyocytes-for-the-assessment-of-drug-induced-proarrhythmic-potential
#8
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
#9
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/27922053/electrophysiological-properties-of-ca1-pyramidal-neurons-along-the-longitudinal-axis-of-the-mouse-hippocampus
#10
Giampaolo Milior, Maria Amalia Di Castro, Livio Pepe' Sciarria, Stefano Garofalo, Igor Branchi, Davide Ragozzino, Cristina Limatola, Laura Maggi
Evidence for different physiological properties along the hippocampal longitudinal axis is emerging. Here, we examined the electrophysiological features of neurons at different dorso-ventral sites of the mouse CA1 hippocampal region. Cell position was defined with respect to longitudinal coordinates of each slice. We measured variations in neuronal excitability, subthreshold membrane properties and neurotransmitter responses along the longitudinal axis. We found that (i) pyramidal cells of the dorsal hippocampus (DH) were less excitable than those of the ventral hippocampus (VH)...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921262/a-new-era-of-disease-modeling-and-drug-discovery-using-induced-pluripotent-stem-cells
#11
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/27920532/the-effect-of-magnetic-nanoparticles-on-neuronal-differentiation-of-induced-pluripotent-stem-cell-derived-neural-precursors
#12
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/27919783/the-potential-of-induced-pluripotent-stem-cells-as-a-tool-to-study-skeletal-dysplasias-and-cartilage-related-pathologic-conditions
#13
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
#14
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/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/27916777/modeling-inherited-arrhythmia-disorders-using-induced-pluripotent-stem-cell-derived-cardiomyocytes
#18
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/27916472/generation-of-neural-cells-using-ipscs-from-sleep-bruxism-patients-with-5-ht2a-polymorphism
#19
Yurie Hoashi, Satoshi Okamoto, Yuka Abe, Takashi Matsumoto, Junichi Tanaka, Yuya Yoshida, Kent Imaizumi, Kenji Mishima, Wado Akamatsu, Hideyuki Okano, Kazuyoshi Baba
PURPOSE: Sleep bruxism (SB) is classified as a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep, which is responsible for a variety of clinical problems such as abnormal tooth attrition and fracture of teeth or roots. Little is known about the etiology of SB. Our previous study identified a genomic association of the serotonin 2A receptor (5-HT2A) single nucleotide polymorphism (SNP), rs6313 C>T, with SB, where the C allele carrier is associated with a 4...
December 1, 2016: Journal of Prosthodontic Research
https://www.readbyqxmd.com/read/27915167/examining-fkbp5-mrna-expression-in-human-ipsc-derived-neural-cells
#20
Richard Lieberman, Henry R Kranzler, Eric S Levine, Jonathan Covault
In peripheral blood leukocytes, FKBP5 mRNA expression is upregulated following glucocorticoid receptor activation. The single nucleotide polymorphism rs1360780 in FKBP5 is associated with psychiatric illness and has functional molecular effects. However, examination of FKBP5 regulation has largely been limited to peripheral cells, which may not reflect regulation in neural cells. We used 27 human induced pluripotent stem cell lines (iPSCs) derived from 20 subjects to examine FKBP5 mRNA expression following GR activation...
November 24, 2016: Psychiatry Research
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