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https://www.readbyqxmd.com/read/28930148/elongation-of-axon-extension-for-human-ipsc-derived-retinal-ganglion-cells-by-a-nano-imprinted-scaffold
#1
Tien-Chun Yang, Jen-Hua Chuang, Waradee Buddhakosai, Wen-Ju Wu, Chen-Ju Lee, Wun-Syuan Chen, Yi-Ping Yang, Ming-Chia Li, Chi-Hsien Peng, Shih-Jen Chen
Optic neuropathies, such as glaucoma and Leber's hereditary optic neuropathy (LHON) lead to retinal ganglion cell (RGC) loss and therefore motivate the application of transplantation technique into disease therapy. However, it is a challenge to direct the transplanted optic nerve axons to the correct location of the retina. The use of appropriate scaffold can promote the proper axon growth. Recently, biocompatible materials have been integrated into the medical field, such as tissue engineering and reconstruction of damaged tissues or organs...
September 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28928965/recent-advances-in-understanding-and-managing-cardiomyopathy
#2
REVIEW
Paulino Alvarez, Wh Wilson Tang
Cardiomyopathy is a disease of the heart muscle leading to abnormal structure or function in the absence of coronary artery disease, hypertension, or valvular or congenital heart disease. Currently, cardiomyopathy is the leading diagnosis of heart transplant patients worldwide. Incorporation of next-generation sequencing strategies will likely revolutionize genetic testing in cardiomyopathy. The use of patient-specific pluripotent stem cell-derived cardiomyocytes for disease modeling and therapeutic testing has opened a new avenue for precision medicine in cardiomyopathy...
2017: F1000Research
https://www.readbyqxmd.com/read/28928383/human-stem-cells-alter-the-invasive-properties-of-somatic-cells-via-paracrine-activation-of-mtorc1
#3
Margit Rosner, Ha Thi Thanh Pham, Richard Moriggl, Markus Hengstschläger
Controlled invasion is essential during many physiological processes, whereas its deregulation is a hallmark of cancer. Here we demonstrate that embryonic, induced pluripotent and amniotic fluid stem cells share the property to induce the invasion of primary somatic cells of various origins through insulin-like growth factor I (IGF-I)- or II (IGF-II)-mediated paracrine activation of mechanistic target of rapamycin complex 1 (mTORC1). We propose a model in which downstream of mTORC1 this stem cell-induced invasion is mediated by hypoxia-inducible factor 1-alpha (HIF-1α)-regulated matrix metalloproteinases...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928053/development-of-correction-formula-for-field-potential-duration-of-human-induced-pluripotent-stem-cell-derived-cardiomyocytes-sheets
#4
Hiroko Izumi-Nakaseko, Yasunari Kanda, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Takeshi Wada, Kentaro Ando, Atsuhiko T Naito, Yuko Sekino, Atsushi Sugiyama
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been used in many studies to assess proarrhythmic risks of chemical compounds. In those studies, field potential durations (FPD) of hiPSC-CMs have been corrected by clinically used Fridericia's and/or Bazett's formulae, however, the rationale for the use of these formulae has not been well established. In the present study, we developed a correction formula for experiments using hiPSC-CMs. First, we analyzed the effect of beating rate on FPD in the hiPSC-CMs sheets with electrical stimuli and a HCN channel inhibitor zatebradine...
September 6, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28927462/generation-of-special-autosomal-dominant-polycystic-kidney-disease-ipscs-with-the-capability-of-functional-kidney-like-cell-differentiation
#5
Jiahui Huang, Shumin Zhou, Xin Niu, Bin Hu, Qing Li, Feng Zhang, Xue Zhang, Xiujuan Cai, Yuanlei Lou, Fen Liu, Chenming Xu, Yang Wang
BACKGROUND: Human induced pluripotent stem cells (iPSCs) have been verified as a powerful cell model for the study of pathogenesis in hereditary disease. Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations of PKD or non-PKD genes. The pathogenesis of ADPKD remains unexplored because of the lack of a true human cell model. METHODS: Six ADPKD patients and four healthy individuals were recruited as donors of somatic cells from a Chinese ADPKD family without mutations of the PKD genes but carrying SAMSN1 gene deletion...
September 19, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28927044/isolation-and-characterization-of-adult-mammary-stem-cells-from-breast-cancer-adjacent-tissues
#6
Ai-Ping Shi, Zhi-Min Fan, Ke-Wei Ma, Yan-Fang Jiang, Lei Wang, Ke-Wei Zhang, Shi-Bo Fu, Ning Xu, Zhi-Ru Zhang
Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926760/laminin-%C3%AE-5-substrates-promote-survival-network-formation-and-functional-development-of-human-pluripotent-stem-cell-derived-neurons-in-vitro
#7
Anu Hyysalo, Mervi Ristola, Meeri E-L Mäkinen, Sergei Häyrynen, Matti Nykter, Susanna Narkilahti
Laminins are one of the major protein groups in the extracellular matrix (ECM) and specific laminin isoforms are crucial for neuronal functions in the central nervous system in vivo. In the present study, we compared recombinant human laminin isoforms (LN211, LN332, LN411, LN511, and LN521) and laminin isoform fragment (LN511-E8) in in vitro cultures of human pluripotent stem cell (hPSC)-derived neurons. We showed that laminin substrates containing the α5-chain are important for neuronal attachment, viability and network formation, as detected by phase contrast imaging, viability staining, and immunocytochemistry...
September 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28926110/pacap-and-pac1r-are-differentially-expressed-in-motor-cortex-of-amyotrophic-lateral-sclerosis-patients-and-support-survival-of-ipsc-derived-motor-neurons
#8
Gabriele Bonaventura, Rosario Iemmolo, Agata Grazia D'Amico, Valentina La Cognata, Erminio Costanzo, Mario Zappia, Velia D'Agata, Francesca Luisa Conforti, Eleonora Aronica, Sebastiano Cavallaro
Amyotrophic lateral sclerosis (ALS) is a fatal and disabling neurodegenerative disease characterized by upper and lower motor neurons depletion. In our previous work, comprehensive genomic profiling of 41 motor cortex samples enabled to discriminate controls from sporadic ALS patients, and segregated these latter into two distinct subgroups (SALS1 and SALS2), each associated with different deregulated genes. In the present study, we focused our attention on two of them, Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its type 1 receptor (PAC1R), and validated the results of the transcriptome experiments by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry and western blot analysis...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925369/generation-of-a-gene-corrected-isogenic-control-ipsc-line-from-cystic-fibrosis-patient-specific-ipscs-homozygous-for-p-phe508del-mutation-mediated-by-talens-and-ssodn
#9
Sylvia Merkert, Christien Bednarski, Gudrun Göhring, Toni Cathomen, Ulrich Martin
Cystic fibrosis (CF) is a monogenetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which affects multiple organs. Human induced pluripotent stem cells (iPSCs) derived from CF patients and the generation of isogeneic gene-corrected control cell lines enable disease modelling, drug discovery or toxicological studies and therefore the development of CF patient-specific therapies. We have previously generated a hiPSC line from a CF patient homozygous for the p...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925368/a-marfan-syndrome-human-induced-pluripotent-stem-cell-line-with-a-heterozygous-fbn1-c-4082g-a-mutation-ismmsi002-b-for-disease-modeling
#10
Sandra Klein, Jill L Dvornik, Akshitha R Yarrabothula, Christoph Schaniel
Fibroblasts of a 28-year-old female with Marfan syndrome (MFS) due to a heterozygous FBN1 c.4082G>A mutation were reprogrammed using the Sendai virus delivery method. The established human induced pluripotent stem cell (hiPSC) line named ISMMSi002-B expresses pluripotency markers, has a normal karyotype, carries the specific FBN1 mutation and is able to differentiate into three germ layers in vitro. ISMMSi002-B has utility in studying MFS pathogenesis, including skeletal abnormalities, cardiomyopathy, and vascular smooth muscle cell dysfunction associated with aortic aneurysm...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925367/generation-of-integration-free-induced-pluripotent-stem-cells-gzhmui001-a-by-reprogramming-peripheral-blood-mononuclear-cells-from-a-47-xxx-syndrome-patient
#11
Yuchang Chen, Zhanhui Ou, Bing Song, Yexing Xian, Shuming Ouyang, Yuhuan Xie, Yanting Xue, Xiaofang Sun
47, XXX syndrome is one of several sex-chromosomal aneuploidies, and it has an incidence of approximately 1/1000 in newborn females. Because of heterogeneity in X-inactivation, these patients may exhibit a variety of clinical symptoms. Here, we report the generation of an integration-free human induced pluripotent stem cell line (GZHMUi001-A) by using Sendai virus to reprogram peripheral blood mononuclear cells from a 47, XXX syndrome patient with premature ovarian failure. This 47, XXX iPS cell line has characteristics of pluripotent stem cells and is a useful tool for the investigation of this X chromosome aneuploid disease...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925365/generation-of-an-induced-pluripotent-stem-cell-ipsc-line-from-a-patient-with-maturity-onset-diabetes-of-the-young-type-13-mody13-with-a-the-potassium-inwardly-rectifying-channel-subfamily-j-member-11-kcnj11-mutation
#12
Frank Griscelli, Olivier Feraud, Tony Ernault, Noufissa Oudrihri, Ali G Turhan, Amélie Bonnefond, Philippe Froguel, Annelise Bennaceur-Griscelli
Heterozygous activating mutation (p.Glu227Lys) in KCNJ11 leads to maturity-onset diabetes of the young (MODY) type 13, that is a subtype of dominant inherited young-onset non-autoimmune diabetes due to a primary defect in pancreatic beta cells. We generated induced pluripotent stem cells (iPSCs) from a patient with KCNJ11(p.Glu227Lys) mutation who developed MODY at 13years old. KCNJ11(p.Glu227Lys)-mutated cells that were reprogrammed by non-integrative viral transduction had normal karyotype, harboured the KCNJ11(p...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925364/generation-and-characterization-of-a-human-ipsc-line-from-a-patient-with-propionic-acidemia-due-to-defects-in-the-pcca-gene
#13
Esmeralda Alonso-Barroso, Sandra Brasil, Álvaro Briso-Montiano, Rosa Navarrete, Celia Pérez-Cerdá, Magdalena Ugarte, Belén Pérez, Lourdes R Desviat, Eva Richard
Human induced pluripotent stem cell (iPSC) line was generated from fibroblasts of a patient with propionic acidemia carrying mutations in the PCCA gene: c.1899+4_1899+7delAGTA; p.(Cys616_Val633del) and c.1430--?_1643+?del; p.(Gly477Glufs*9). Reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC were delivered using a non-integrative method based on the Sendai virus. Once established, iPSCs have shown full pluripotency, differentiation capacity and genetic stability.
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925363/generation-of-an-induced-pluripotent-stem-cell-line-from-a-patient-with-hereditary-multiple-endocrine-neoplasia-2b-men2b-syndrome-with-highest-risk-ret-mutation
#14
A Bennaceur-Griscelli, J Hadoux, O Féraud, P Opolon, D Divers, E Gobbo, M Schlumberger, F Griscelli, A G Turhan
Multiple Endocrine Neoplasia Type 2B (MEN2B) is a cancer-predisposing syndrome that affects patients with germline RET mutations. The clinical spectrum of the syndrome includes medullary thyroid carcinoma (MTC) and pheochromocytoma. Currently, there is no satisfactory model recapitulating all the features of the disease especially at the level of stem cells. We generated induced pluripotent stem cells (iPSCs) from a patient with RET mutation at codon 918 who developed pheochromocytoma and MTC. These iPSC had normal karyotype, harboured the RET(M918T) mutation and expressed pluripotency hallmarks...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925362/generation-of-a-klf15-homozygous-knockout-human-embryonic-stem-cell-line-using-paired-crispr-cas9n-and-human-cardiomyocytes-derivation
#15
Claudia Noack, Luis Peter Haupt, Wolfram-Hubertus Zimmermann, Katrin Streckfuss-Bömeke, Laura Cecilia Zelarayán
Krueppel-like factor 15 (KLF15) is abundantly expressed in liver, kidney, and muscle, including myocardium. In the adult heart KLF15 is important to maintain homeostasis and to repress hypertrophic remodeling. We generated a homozygous hESC KLF15 knockout (KO) line using paired CRISPR/Cas9n. KLF15-KO cells maintained full pluripotency and differentiation potential as well as genomic integrity. We demonstrated that KLF15-KO cells can be differentiated into morphologically normal cardiomyocytes turning them into a valuable tool for studying human KLF15-mediated mechanisms resulting in human cardiac dysfunction...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925360/establishment-of-an-induced-pluripotent-stem-cell-line-zzui003-a-from-a-65-year-old-male-with-sporadic-parkinson-s-disease
#16
Xiangyu Zheng, Zhiqiang Zhu, Kuisheng Chen, Shewei Guo, Tiantian Liu, Hongfang Liu
Skin fibroblasts were collected from a 65-year-old male patient with sporadic Parkinson's disease. Induced pluripotent stem cells were reprogrammed with human reprogramming factors (KMOSL) using the messenger RNA reprogramming protocol. The transgene-free iPSC line showed pluripotency, displayed normal karyotype, and could form embryoid bodies in vitro and differentiate into all 3 germ layers in vivo. This iPSC line can be a useful cellular model for studying the mechanism of Parkinson's disease.
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28925359/generation-of-an-oct4-reporter-human-induced-pluripotent-stem-cell-line-using-crispr-spcas9
#17
Diego Balboa, Jere Weltner, Yuval Novik, Solja Eurola, Kirmo Wartiovaara, Timo Otonkoski
OCT4 is a crucial transcription factor in the pluripotent stem cell gene regulatory network and an essential factor for pluripotent reprogramming. We engineered the previously reported HEL24.3 hiPSC to generate an OCT4 reporter cell line by knocking-in a T2A nuclear EmGFP reporter cassette before the OCT4 gene STOP codon sequence. To enhance targeted insertion, homologous recombination was stimulated using targeted cutting at the OCT4 STOP codon with CRISPR/SpCas9. This HEL24.3-OCT4-nEmGFP cell line faithfully reports endogenous OCT4 expression, serving as a useful tool to examine temporal changes in OCT4 expression in live cells during hiPSC culture, differentiation and somatic cell reprogramming...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28924979/quantification-of-etoposide-hypersensitivity-a-sensitive-functional-method-for-assessing-pluripotent-stem-cell-quality
#18
Frank J Secreto, Xing Li, Alyson J Smith, Elizabeth S Bruinsma, Ester Perales-Clemente, Saji Oommen, Gresin Hawse, Sybil C L Hrstka, Bonnie K Arendt, Emma B Brandt, Dennis A Wigle, Timothy J Nelson
Human induced pluripotent stem cells (hiPSC) hold great promise in diagnostic and therapeutic applications. However, translation of hiPSC technology depends upon a means of assessing hiPSC quality that is quantitative, high-throughput, and can decipher malignant teratocarcinoma clones from normal cell lines. These attributes are lacking in current approaches such as detection of cell surface makers, RNA profiling, and/or teratoma formation assays. The latter remains the gold standard for assessing clone quality in hiPSCs, but is expensive, time-consuming, and incompatible with high-throughput platforms...
September 19, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28924210/kinase-inhibitor-screening-using-artificial-neural-networks-and-engineered-cardiac-biowires
#19
Genevieve Conant, Samad Ahadian, Yimu Zhao, Milica Radisic
Kinase inhibitors are often used as cancer targeting agents for their ability to prevent the activation of cell growth and proliferation signals. Cardiotoxic effects have been identified for some marketed kinase inhibitors that were not detected during clinical trials. We hypothesize that more predictive cardiac functional assessments of kinase inhibitors on human myocardium can be established by combining a high-throughput two-dimensional (2D) screening assay and a high-content three-dimensional (3D) engineered cardiac tissue (Biowire(TM)) based assay, and using human induced pluripotent stem cell-derived CMs (hiPSC-CMs)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924182/an-in-vitro-model-of-lissencephaly-expanding-the-role-of-dcx-during-neurogenesis
#20
M Shahsavani, R J Pronk, R Falk, M Lam, M Moslem, S B Linker, J Salma, K Day, J Schuster, B-M Anderlid, N Dahl, F H Gage, A Falk
Lissencephaly comprises a spectrum of brain malformations due to impaired neuronal migration in the developing cerebral cortex. Classical lissencephaly is characterized by smooth cerebral surface and cortical thickening that result in seizures, severe neurological impairment and developmental delay. Mutations in the X-chromosomal gene DCX, encoding doublecortin, is the main cause of classical lissencephaly. Much of our knowledge about DCX-associated lissencephaly comes from post-mortem analyses of patient's brains, mainly since animal models with DCX mutations do not mimic the disease...
September 19, 2017: Molecular Psychiatry
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