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Induced pluripotent stem

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https://www.readbyqxmd.com/read/28107800/neuroregeneration-of-ips-cells-in-polyacrylamide-chitosan-inverted-colloidal-crystal-scaffolds-with-poly-lactide-co-glycolide-nanoparticles-and-tatvhl-peptide
#1
Yung-Chih Kuo, Chun-Wei Chen
Polyacrylamide (PAAM) and chitosan were fabricated by inverted colloidal crystal (ICC) method for scaffolds comprising regular pores. The hybrid PAAM-chitosan ICC scaffolds were grafted with poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) for a rougher pore surface and grafted with TATVHL peptide for a better differentiation of induced pluripotent stem (iPS) cells toward neural lineage. By scanning electron microscopy, we found that iPS cells cultured in PAAM-chitosan ICC scaffolds with PLGA NPs at 1...
January 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28107504/sox10-nano-lantern-reporter-human-ips-cells-a-versatile-tool-for-neural-crest-research
#2
Tomoko Horikiri, Hiromi Ohi, Mitsuaki Shibata, Makoto Ikeya, Morio Ueno, Chie Sotozono, Shigeru Kinoshita, Takahiko Sato
The neural crest is a source to produce multipotent neural crest stem cells that have a potential to differentiate into diverse cell types. The transcription factor SOX10 is expressed through early neural crest progenitors and stem cells in vertebrates. Here we report the generation of SOX10-Nano-lantern (NL) reporter human induced pluripotent stem cells (hiPS) by using CRISPR/Cas9 systems, that are beneficial to investigate the generation and maintenance of neural crest progenitor cells. SOX10-NL positive cells are produced transiently from hiPS cells by treatment with TGFβ inhibitor SB431542 and GSK3 inhibitor CHIR99021...
2017: PloS One
https://www.readbyqxmd.com/read/28107356/integrity-of-induced-pluripotent-stem-cell-ipsc-derived-megakaryocytes-as-assessed-by-genetic-and-transcriptomic-analysis
#3
Kai Kammers, Margaret A Taub, Ingo Ruczinski, Joshua Martin, Lisa R Yanek, Alyssa Frazee, Yongxing Gao, Dixie Hoyle, Nauder Faraday, Diane M Becker, Linzhao Cheng, Zack Z Wang, Jeff T Leek, Lewis C Becker, Rasika A Mathias
Previously, we have described our feeder-free, xeno-free approach to generate megakaryocytes (MKs) in culture from human induced pluripotent stem cells (iPSCs). Here, we focus specifically on the integrity of these MKs using: (1) genotype discordance between parent cell DNA to iPSC cell DNA and onward to the differentiated MK DNA; (2) genomic structural integrity using copy number variation (CNV); and (3) transcriptomic signatures of the derived MK lines compared to the iPSC lines. We detected a very low rate of genotype discordance; estimates were 0...
2017: PloS One
https://www.readbyqxmd.com/read/28106276/crispr-cas9-mediated-deletion-of-c1eis-inhibits-chicken-embryonic-stem-cell-differentiation-into-male-germ-cells-gallus-gallus
#4
Qisheng Zuo, Kai Jin, Yingjie Wang, Jiuzhou Song, Yani Zhang, Bichun Li
We previously found that C1EIS is preferentially expressed in Chicken spermatogonial stem cells (SSCs) by RNA sequencing (RNA-seq), so our current study focused on C1EIS's role in Chicken embryonic stem cells (ESCs) differentiation into male germ cells. We constructed a CRISPR/Cas9 vector targeting C1EIS. T7 endonuclease I (T7EI) digestion method and sequencing of TA cloning were used to detect the knock-out efficiency of the Single guide RNA (sgRNA) after the cas9/gRNA vector transfected into D fibroblasts 1(DF-1), ESCs and Chicken embryos...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28104773/exosomes-generated-from-ipsc-derivatives-new-direction-for-stem-cell-therapy-in-human-heart-diseases
#5
REVIEW
Ji-Hye Jung, Xuebin Fu, Phillip C Yang
Cardiovascular disease (CVD) is the leading cause of death in modern society. The adult heart innately lacks the capacity to repair and regenerate the damaged myocardium from ischemic injury. Limited understanding of cardiac tissue repair process hampers the development of effective therapeutic solutions to treat CVD such as ischemic cardiomyopathy. In recent years, rapid emergence of induced pluripotent stem cells (iPSC) and iPSC-derived cardiomyocytes presents a valuable opportunity to replenish the functional cells to the heart...
January 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28103772/induced-pluripotency-and-gene-editing-in-fanconi-anemia
#6
Susana Navarro, Alessandra Giorgetti, Angel Raya, Jakub Tolar
Induced pluripotent stem cells (iPSCs) represent an invaluable tool in a chromosomal instability syndrome such as Fanconi anemia (FA), as they can allow study of the molecular defects underlying this disease. Many other applications, such as its use as a platform to test different methods or compounds, could also be of interest. But the greatest impact of iPSCs may be in bone marrow failure diseases, as iPSCs could represent an unlimited source of autologous cells to apply in advanced treatments such as gene therapy...
January 18, 2017: Current Gene Therapy
https://www.readbyqxmd.com/read/28103756/compression-induced-chondrogenic-differentiation-of-embryonic-stem-cells-in-3-d-pdms-scaffolds
#7
Christina McKee, Yifeng Hong, Donggang Yao, G Rasul Chaudhry
Embryonic stem cells (ESCs) are an ideal source for chondrogenic progenitors for the repair of damaged cartilage tissue. It is currently difficult to induce uniform and scalable ESC differentiation in vitro, a process required for stem cell therapy. This is partly because stem cell fate is determined by complex interactions with the native microenvironment and mechanical properties of the extracellular matrix. Mechanical signaling is considered to be one of the major factors regulating the proliferation and differentiation of chondrogenic cells both in vitro and in vivo...
January 19, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28102837/precise-and-efficient-scarless-genome-editing-in-stem-cells-using-correct
#8
Dylan Kwart, Dominik Paquet, Shaun Teo, Marc Tessier-Lavigne
CRISPR/Cas9 is a promising tool for genome-editing DNA in cells with single-base-pair precision, which allows novel in vitro models of human disease to be generated-e.g., in pluripotent stem cells. However, the accuracy of intended sequence changes can be severely diminished by CRISPR/Cas9's propensity to re-edit previously modified loci, causing unwanted mutations (indels) alongside intended changes. Here we describe a genome-editing framework termed consecutive re-guide or re-Cas steps to erase CRISPR/Cas-blocked targets (CORRECT), which, by exploiting the use of highly efficacious CRISPR/Cas-blocking mutations in two rounds of genome editing, enables accurate, efficient and scarless introduction of specific base changes-for example, in human induced pluripotent (iPS) stem cells...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28100040/induced-pluripotent-stem-cell-research-in-the-era-of-precision-medicine
#9
Takashi Hamazaki, Nihal El Rouby, Natalie C Fredette, Katherine E Santostefano, Naohiro Terada
Recent advances in DNA sequencing technologies are revealing how human genetic variations associate with differential health risks, disease susceptibilities and drug responses. Such information is now expected to help evaluate individual health risks, design personalized health plans and treat patients with precision. It is still challenging, however, to understand how such genetic variations cause the phenotypic alterations in pathobiologies and treatment response. Human induced pluripotent stem cell (iPSC) technologies are emerging as a promising strategy to fill the knowledge gaps between genetic association studies and underlying molecular mechanisms...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28100021/identifying-the-biphasic-role-of-calcineurin-nfat-signaling-enables-replacement-of-sox2-in-somatic-cell-reprogramming
#10
Sherif Khodeer, Takumi Era
Induction of pluripotency with defined factors (Oct4, Sox2, Klf4, c-Myc) raises hopes for successful clinical trials. Despite considerable efforts, the molecular mechanism of reprogramming remains poorly understood. The aim of the present study was to identify the role of calcineurin/nuclear factor of activated T cells (NFAT) in reprogramming. Our results demonstrated a biphasic role for calcineurin/NFAT signaling during reprogramming. In the early phase of reprogramming, calcineurin activity is required to maintain proper cell cycle division and for mesenchymal-epithelial transition...
January 18, 2017: Stem Cells
https://www.readbyqxmd.com/read/28098961/angiogenic-and-osteogenic-regeneration-in-rats-via-calcium-phosphate-scaffold-and-endothelial-cell-coculture-with-hbmscs-hucmscs-hipsc-mscs-and-hesc-mscs
#11
Wenchuan Chen, Xian Liu, Qianmin Chen, Chongyun Bao, Liang Zhao, Zhimin Zhu, Hockin H K Xu
Angiogenesis is a limiting factor in regenerating large bone defects. The objective of this study was to investigate angiogenic and osteogenic effects of coculture on calcium phosphate cement (CPC) scaffold using human umbilical vein endothelial cells (hUVECs) and mesenchymal stem cells (MSCs) from different origins for the first time. hUVECs were cocultured with four types of cells: human umbilical cord MSCs (hUCMSCs), human bone marrow MSCs (hBMSCs), and MSCs from induced pluripotent stem cells (hiPSC-MSCs) and embryonic stem cells (hESC-MSCs)...
January 18, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28097777/activin-a-in-combination-with-erk1-2-mapk-pathway-inhibition-sustains-propagation-of-mouse-embryonic-stem-cells
#12
Yuhei Ashida, May Nakajima-Koyama, Akira Hirota, Takuya Yamamoto, Eisuke Nishida
The Activin/Nodal/TGF-β signaling pathway plays a major role in maintaining mouse epiblast stem cells (EpiSCs). The EpiSC-maintaining medium, which contains Activin A and bFGF, induces differentiation of mouse embryonic stem cells (ESCs) to EpiSCs. Here, we show that Activin A also has an ability to efficiently propagate ESCs without differentiation to EpiSCs when combined with a MEK inhibitor PD0325901. ESCs cultured in Activin+PD retained high-level expression of naive pluripotency-related transcription factors...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28096185/transcriptomic-profiling-of-purified-patient-derived-dopamine-neurons-identifies-convergent-perturbations-and-therapeutics-for-parkinson-s-disease
#13
Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley, Richard Wade-Martins, Caleb Webber
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes...
January 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28094846/chronic-drug-induced-effects-on-contractile-motion-properties-and-cardiac-biomarkers-in-human-induced-pluripotent-stem-cell-derived-cardiomyocytes
#14
Ivan Kopljar, An De Bondt, Petra Vinken, Ard Teisman, Bruce Damiano, Nick Goeminne, Ilse Van den Wyngaert, David J Gallacher, Hua Rong Lu
BACKGROUND AND PURPOSE: Risk assessment of chronic cardiac safety liabilities within the pharmaceutical industry is mostly performed during late stages of pre-clinical drug development using in vivo animal models. Here, we explored the potential of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to detect chronic cardiac risks such as drug-induced cardiomyocyte toxicity. EXPERIMENTAL APPROACH: Video microscopy-based motion field imaging was applied to evaluate chronic effect (over 72 h) of cardiotoxic drugs on the contractile motion of hiPS-CMs...
January 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28093354/low-dose-resveratrol-ameliorates-mitochondrial-respiratory-dysfunction-and-enhances-cellular-reprogramming
#15
Yuki Mizuguchi, Hideyuki Hatakeyama, Kou Sueoka, Mamoru Tanaka, Yu-Ichi Goto
Mitochondrial disease is associated with a wide variety of clinical presentations, even among patients carrying heteroplasmic mitochondrial DNA (mtDNA) mutations, probably because of variations in mutant mtDNA proportions at the tissue and organ levels. Although several case reports and clinical trials have assessed the effectiveness of various types of drugs and supplements for the treatment of mitochondrial diseases, there are currently no cures for these conditions. In this study, we demonstrated for the first time that low dose resveratrol (RSV) ameliorated mitochondrial respiratory dysfunction in patient-derived fibroblasts carrying homoplasmic mtDNA mutations...
January 13, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28092949/label-free-separation-of-induced-pluripotent-stem-cells-with-anti-ssea-1-antibody-immobilized-microfluidic-channel
#16
Akihisa Otaka, Kazuki Kitagawa, Takahiko Nakaoki, Mitsuhi Hirata, Kyoko Fukazawa, Kazuhiko Ishihara, Atsushi Mahara, Tetsuji Yamaoka
When induced pluripotent stem cell (iPSC) is routinely cultured, the obtained cells are a heterogeneous mixture, including feeder cells and partially differentiated cells. Therefore, a purification process is required to use them in a clinical stage. We described a label-free separation of iPSCs using a microfluidic channel. Antibodies against stage-specific embryonic antigen 1 (SSEA-1) was covalently immobilized on the channel coated with a phospholipid polymer. After injection of the heterogeneous cell suspension containing iPSCs, the velocity of cell movement under a liquid flow condition was measured...
January 16, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28092083/role-of-dopamine-d2-d3-receptors-in-development-plasticity-and-neuroprotection-in-human-ipsc-derived-midbrain-dopaminergic-neurons
#17
Federica Bono, Paola Savoia, Adele Guglielmi, Massimo Gennarelli, Giovanna Piovani, Sandra Sigala, Damiana Leo, Stefano Espinoza, Raul R Gainetdinov, Paola Devoto, PierFranco Spano, Cristina Missale, Chiara Fiorentini
The role of dopamine D2 and D3 receptors (D2R/D3R), located on midbrain dopaminergic (DA) neurons, in the regulation of DA synthesis and release and in DA neuron homeostasis has been extensively investigated in rodent animal models. By contrast, the properties of D2R/D3R in human DA neurons have not been elucidated yet. On this line, the use of human-induced pluripotent stem cells (hiPSCs) for producing any types of cells has offered the innovative opportunity for investigating the human neuronal phenotypes at the molecular levels...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28091967/balancing-ethical-pros-and-cons-of-stem-cell-derived-gametes
#18
Seppe Segers, Heidi Mertes, Guido de Wert, Wybo Dondorp, Guido Pennings
In this review we aim to provide an overview of the most important ethical pros and cons of stem cell derived gametes (SCD-gametes), as a contribution to the debate about reproductive tissue engineering. Derivation of gametes from stem cells holds promising applications both for research and for clinical use in assisted reproduction. We explore the ethical issues connected to gametes derived from embryonic stem cells (both patient specific and non-patient specific) as well as those related to gametes derived from induced pluripotent stem cells...
January 13, 2017: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/28090699/modelling-irf8-deficient-human-hematopoiesis-and-dendritic-cell-development-with-engineered-ips-cells
#19
Stephanie Sontag, Malrun Förster, Jie Qin, Paul Wanek, Saskia Mitzka, Herdit M Schüler, Steffen Koschmieder, Stefan Rose-John, Kristin Seré, Martin Zenke
Human induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers, including hematopoietic stem cells and their progeny. Interferon regulatory factor 8 (IRF8) is a transcription factor, which acts in hematopoiesis as lineage determining factor for myeloid cells, including dendritic cells (DC). Autosomal recessive or dominant IRF8 mutations occurring in patients cause severe monocytic and DC immunodeficiency. To study IRF8 in human hematopoiesis we generated human IRF8-/- iPS cells and IRF8-/- embryonic stem (ES) cells using RNA guided CRISPR/Cas9n genome editing...
January 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28090031/differentiation-behavior-of-ips-cells-cultured-on-plga-with-osteoinduction-medium
#20
Reiko Tokita, Kei Nakajima, Kenji Inoue, Akram Al-Wahabi, Tungalag Ser-Od, Kenichi Matsuzaka, Takashi Inoue
In the present report, we have generated osteoblast-like cells derived from mouse induced-pluripotent stem (iPS) cells on PLGA with osteoinduction medium in vitro and in vivo. The cell culture period was 2 weeks. At 2 weeks, mRNA level of type I collagen was significantly higher than at 1 week. Osteocalcin mRNA level at 2 weeks was tendency to increase compared with at 1 week. And the cells cultured on PLGA were positive for immunofluorescent staining of osteocalcin and alizarin red S staining. The scaffold and osteogenic-like cells induced in vitro were implanted subcutaneously into SCID mice...
January 13, 2017: Dental Materials Journal
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