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Induced pluripotent cells

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https://www.readbyqxmd.com/read/28654420/lineage-commitment-of-embryonic-cells-involves-mek1-dependent-clearance-of-pluripotency-regulator-ventx2
#1
Pierluigi Scerbo, Leslie Marchal, Laurent Kodjabachian
During early embryogenesis, cells must exit pluripotency and commit to multiple lineages in all germ-layers. How this transition is operated in vivo is poorly understood. Here, we report that MEK1 and the Nanog-related transcription factor Ventx2 coordinate this transition. MEK1 was required to make Xenopus pluripotent cells competent to respond to all cell fate inducers tested. Importantly, MEK1 activity was necessary to clear the pluripotency protein Ventx2 at the onset of gastrulation. Thus, concomitant MEK1 and Ventx2 knockdown restored the competence of embryonic cells to differentiate...
June 27, 2017: ELife
https://www.readbyqxmd.com/read/28654077/protocol-for-the-differentiation-of-human-induced-pluripotent-stem-cells-into-mixed-cultures-of-neurons-and-glia-for-neurotoxicity-testing
#2
Francesca Pistollato, David Canovas-Jorda, Dimitra Zagoura, Anna Price
Human pluripotent stem cells can differentiate into various cell types that can be applied to human-based in vitro toxicity assays. One major advantage is that the reprogramming of somatic cells to produce human induced pluripotent stem cells (hiPSCs) avoids the ethical and legislative issues related to the use of human embryonic stem cells (hESCs). HiPSCs can be expanded and efficiently differentiated into different types of neuronal and glial cells, serving as test systems for toxicity testing and, in particular, for the assessment of different pathways involved in neurotoxicity...
June 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28654049/chondrogenic-pellet-formation-from-cord-blood-derived-induced-pluripotent-stem-cells
#3
Yoojun Nam, Yeri Alice Rim, Ji Hyeon Ju
Human articular cartilage lacks the ability to repair itself. Cartilage degeneration is thus treated not by curative but by conservative treatments. Currently, efforts are being made to regenerate damaged cartilage with ex vivo expanded chondrocytes or bone marrow-derived mesenchymal stem cells (BMSCs). However, the restricted viability and instability of these cells limit their application in cartilage reconstruction. Human induced pluripotent stem cells (hiPSCs) have received scientific attention as a new alternative for regenerative applications...
June 19, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28651900/potential-clinical-applications-of-placental-stem-cells-for-use-in-fetal-therapy-of-birth-defects
#4
Melissa Vanover, Aijun Wang, Diana Farmer
Placental stem cells are of growing interest for a variety of clinical applications due to their multipotency and ready availability from otherwise frequently discarded biomaterial. Stem cells derived from the placenta have been investigated in a number of disease processes, including wound healing, ischemic heart disease, autoimmune disorders, and chronic lung or liver injury. Fetal intervention for structural congenital defects, such as spina bifida, has rapidly progressed as a field due to advances in maternal-fetal medicine and improving surgical techniques...
May 18, 2017: Placenta
https://www.readbyqxmd.com/read/28651685/erratum-to-ganglioside-gm1-influences-the-proliferation-rate-of-mouse-induced-pluripotent-stem-cells
#5
Jae-Sung Ryu, Kyu-Tae Chang, Ju-Taek Lee, Malg-Um Lim, Hyun-Ki Min, Yoon-Ju Na, Su-Bin Lee, Gislain Moussavou, Sun-Uk Kim, Ji-Su Kim, Kinarm Ko, Kisung Ko, Kyung-A Hwang, Eun-Jeong Jeong, Jeong-Woong Lee, Young-Kug Choo
The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 45(12), 713-718 titled "Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells".
June 2017: BMB Reports
https://www.readbyqxmd.com/read/28648896/inhibition-of-cdk5-alleviates-the-cardiac-phenotypes-in-timothy-syndrome
#6
LouJin Song, Seon-Hye E Park, Yehuda Isseroff, Kumi Morikawa, Masayuki Yazawa
L-type calcium channel CaV1.2 plays an essential role in cardiac function. The gain-of-function mutations in CaV1.2 have been reported to be associated with Timothy syndrome, a disease characterized by QT prolongation and syndactyly. Previously we demonstrated that roscovitine, a cyclin-dependent kinase (CDK) inhibitor, could rescue the phenotypes in induced pluripotent stem cell-derived cardiomyocytes from Timothy syndrome patients. However, exactly how roscovitine rescued the phenotypes remained unclear. Here we report a mechanism potentially underlying the therapeutic effects of roscovitine on Timothy syndrome cardiomyocytes...
June 21, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28648749/transcriptome-profiling-of-3d-co-cultured-cardiomyocytes-and-endothelial-cells-under-oxidative-stress-using-a-photocrosslinkable-hydrogel-system
#7
Xiaoshan Yue, Aylin Acun, Pinar Zorlutuna
Myocardial infarction (MI) is one of the most common among cardiovascular diseases. Endothelial cells (ECs) are considered to have protective effects on cardiomyocytes (CMs) under stress conditions such as MI; however, the paracrine CM-EC crosstalk and the resulting endogenous cellular responses that could contribute to this protective effect are not thoroughly investigated. Here we created biomimetic synthetic tissues containing CMs and human induced pluripotent stem cell (hiPSC)-derived ECs (iECs), which showed improved cell survival compared to single cultures under conditions mimicking the aftermath of MI, and performed high-throughput RNA-sequencing to identify target pathways that could govern CM-iEC crosstalk and the resulting improvement in cell viability...
June 22, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28648462/cyclic-tetrapeptide-hdac-inhibitors-as-potential-therapeutics-for-spinal-muscular-atrophy-screening-with-ipsc-derived-neuronal-cells
#8
Jiun-I Lai, Luke J Leman, Sherman Ku, Chris J Vickers, Christian A Olsen, Ana Montero, M Reza Ghadiri, Joel M Gottesfeld
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that is caused by inactivating mutations in the Survival of motor neuron 1 (SMN1) gene, resulting in decreased SMN protein expression. Humans possess a paralog gene, SMN2, which contains a splicing defect in exon 7 leading to diminished expression of full-length, fully functional SMN protein. Increasing SMN2 expression has been a focus of therapeutic development for SMA. Multiple studies have reported the efficacy of histone deacetylase inhibitors (HDACi) in this regard...
June 10, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28648365/direct-reprogramming-of-fibroblasts-via-a-chemically-induced-xen-like-state
#9
Xiang Li, Defang Liu, Yantao Ma, Xiaomin Du, Junzhan Jing, Lipeng Wang, Bingqing Xie, Da Sun, Shaoqiang Sun, Xueqin Jin, Xu Zhang, Ting Zhao, Jingyang Guan, Zexuan Yi, Weifeng Lai, Ping Zheng, Zhuo Huang, Yanzhong Chang, Zhen Chai, Jun Xu, Hongkui Deng
Direct lineage reprogramming, including with small molecules, has emerged as a promising approach for generating desired cell types. We recently found that during chemical induction of induced pluripotent stem cells (iPSCs) from mouse fibroblasts, cells pass through an extra-embryonic endoderm (XEN)-like state. Here, we show that these chemically induced XEN-like cells can also be induced to directly reprogram into functional neurons, bypassing the pluripotent state. The induced neurons possess neuron-specific expression profiles, form functional synapses in culture, and further mature after transplantation into the adult mouse brain...
June 20, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28647433/targeted-release-of-transcription-factors-for-human-cell-reprogramming-by-zebra-cell-penetrating-peptide
#10
Benjamin Caulier, Lionel Berthoin, Helène Coradin, Frédéric Garban, Marie Claire Dagher, Benoît Polack, Bertrand Toussaint, Jean Luc Lenormand, David Laurin
Transcription factors (TFs) are key actors of the control of gene expression and consequently of every major process within cells, ranging from cell fate determination, cell cycle control and response to environment. Their ectopic expression has proven high potential in reprogramming cells for regenerative medicine; ontogenesis studies and cell based modelling. Direct delivery of proteins could represent an alternative to current reprogramming methods using gene transfer but still needs technological improvements...
June 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28646660/towards-understanding-transcriptional-networks-in-cellular-reprogramming
#11
REVIEW
Jaber Firas, Jose M Polo
Most of the knowledge we have on the molecular mechanisms of transcription factor mediated reprogramming comes from studies conducted in induced pluripotency. Recently however, a few studies investigated the mechanisms of cellular reprogramming in direct and indirect transdifferentiation, which allows us to explore whether shared parallel mechanisms can be drawn. Moreover, there are currently several computational tools that have been developed to predict and enhance the reprogramming process by reconstructing the transcriptional networks of reprogramming cells...
June 21, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#12
Claudia Wing, Masaaki Komatsu, Shannon M Delaney, Matthew Krause, Heather E Wheeler, M Eileen Dolan
The generation of induced pluripotent stem cells (iPSCs) and differentiation to cells composing major organs has opened up the possibility for a new model system to study adverse toxicities associated with chemotherapy. Therefore, we used human iPSC-derived neurons to study peripheral neuropathy, one of the most common adverse effects of chemotherapy and cause for dose reduction. To determine the utility of these neurons in investigating the effects of neurotoxic chemotherapy, we measured morphological differences in neurite outgrowth, cell viability as determined by ATP levels and apoptosis through measures of caspase 3/7 activation following treatment with clinically relevant concentrations of platinating agents (cisplatin, oxaliplatin and carboplatin), taxanes (paclitaxel, docetaxel and nab-paclitaxel), a targeted proteasome inhibitor (bortezomib), an antiangiogenic compound (thalidomide), and 5-fluorouracil, a chemotherapeutic that does not cause neuropathy...
June 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28644953/helping-induced-hpscs-clean-up-their-act
#13
Ho-Chang Jeong, Hyuk-Jin Cha
Inhibition of the tumorigenic potential of human pluripotent stem cells (hPSCs) remains critically important for safe hPSC-based therapy. In this issue of Cell Chemical Biology, Kuang et al. (2017) reveal that the phospho-D-peptide D-3 efficiently induces death of residual hPSCs, but not of differentiated progenies, through high alkaline phosphatase activity in hPSCs.
June 22, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28643534/transplantation-of-mouse-induced-pluripotent-stem-cells-into-the-cochlea-for-the-treatment-of-sensorineural-hearing-loss
#14
Jing Chen, Lina Guan, Hengtao Zhu, Shan Xiong, Liang Zeng, Hongqun Jiang
CONCLUSION: Mouse-induced pluripotent stem cells (iPSCs) could differentiate into hair cell-like cells and spiral ganglion-like cells after transplantation into mouse cochleae, but it cannot improve the auditory brain response (ABR) thresholds in short term. OBJECTIVE: To evaluate the potential of iPSCs for use as a source of transplants for the treatment of sensorineural hearing loss (SNHL). METHODS: Establishing SNHL mice model, then injecting the iPSCs or equal volume DMEM basic medium into the cochleae, respectively...
June 23, 2017: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/28643455/pathways-governing-development-of-stem-cell-derived-pancreatic-%C3%AE-cells-lessons-from-embryogenesis
#15
Sara Al-Khawaga, Bushra Memon, Alexandra E Butler, Shahrad Taheri, Abdul B Abou-Samra, Essam M Abdelalim
The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies...
June 22, 2017: Biological Reviews of the Cambridge Philosophical Society
https://www.readbyqxmd.com/read/28643190/mitochondrial-biogenesis-and-neural-differentiation-of-human-ipsc-is-modulated-by-idebenone-in-a-developmental-stage-dependent-manner
#16
J Augustyniak, J Lenart, M Zychowicz, P P Stepien, L Buzanska
Idebenone, the synthetic analog of coenzyme Q10 can improve electron transport in mitochondria. Therefore, it is used in the treatment of Alzheimer's disease and other cognitive impairments. However, the mechanism of its action on neurodevelopment is still to be elucidated. Here we demonstrate that the cellular response of human induced pluripotent stem cells (hiPSC) to idebenone depends on the stage of neural differentiation. When: neural stem cells (NSC), early neural progenitors (eNP) and advanced neural progenitors (NP) have been studied a significant stimulation of mitochondrial biogenesis was observed only at the eNP stage of development...
June 22, 2017: Biogerontology
https://www.readbyqxmd.com/read/28641963/modulation-of-the-heart-s-electrical-properties-by-the-anticonvulsant-drug-retigabine
#17
Lena Rubi, Michael Kovar, Eva Zebedin-Brandl, Xaver Koenig, Manuel Dominguez-Rodriguez, Hannes Todt, Helmut Kubista, Stefan Boehm, Karlheinz Hilber
Retigabine, currently used as antiepileptic drug, has a wide range of potential medical uses. Administration of the drug in patients can lead to QT interval prolongation in the electrocardiogram and to cardiac arrhythmias in rare cases. This suggests that the drug may perturb the electrical properties of the heart, and the underlying mechanisms were investigated here. Effects of retigabine on currents through human cardiac ion channels, heterologously expressed in tsA-201 cells, were studied in whole-cell patch-clamp experiments...
June 19, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28641519/neural-stem-cells-and-human-induced-pluripotent-stem-cells-to-model-rare-cns-diseases
#18
Lidia De Filippis, Cristina Zalfa, Daniela Ferrari
Despite the great effort spent over the last decades to unravel the pathological mechanisms underpinning the development of central nervous system disorders, most of them remain still unclear. In particular, the study of rare brain diseases is hurdled by the lack of post-mortem samples and of reliable epidemiological studies, thus the setting of in vitro modeling systems appears essential to dissect the puzzle of genetic and environmental alterations affecting neural cells viability and functionality The isolation and expansion in vitro of embryonic (ESC) and fetal neural stem cells (NSC) from human tissue has efficiently allowed to model several neurological diseases "in a dish" and has also provided a novel platform to test potential therapeutic strategies in a pre-clinical setting...
June 15, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28640863/induced-pluripotent-stem-cell-derived-limbal-epithelial-cells-lipsc-as-a-cellular-alternative-for-in-vitro-ocular-toxicity-testing
#19
Edith Aberdam, Isabelle Petit, Linda Sangari, Daniel Aberdam
Induced pluripotent stem cells hold great potential to produce unlimited amount of differentiated cells as cellular source for regenerative medicine but also for in vitro drug screening and cytotoxicity tests. Ocular toxicity testing is mandatory to evaluate the risks of drugs and cosmetic products before their application to human patients by preventing eye irritation or insult. Since the global ban to use animals, many human-derived alternatives have been proposed, from ex-vivo enucleated postmortem cornea, primary corneal cell culture and immortalized corneal epithelial cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28640507/a-liver-specific-gene-expression-panel-predicts-the-differentiation-status-of-in-vitro-hepatocyte-models
#20
Dae-Soo Kim, Jea-Woon Ryu, Mi-Young Son, Jung-Hwa Oh, Kyung-Sook Chung, Sugi Lee, Jeong-Ju Lee, Jun-Ho Ahn, Ju-Sik Min, Jiwon Ahn, Hyun Mi Kang, Janghwan Kim, Cho-Rok Jung, Nam-Soon Kim, Hyun-Soo Cho
Alternative cell sources, such as three-dimensional organoids and induced pluripotent stem cell-derived cells, might provide a potentially effective approach for both drug development applications and clinical transplantation. For example, the development of cell sources for liver cell-based therapy has been increasingly needed, and liver transplantation is performed for the treatment for patients with severe end-stage liver disease. Differentiated liver cells and three-dimensional (3D) organoids are expected to provide new cell sources for tissue models and revolutionary clinical therapies...
June 22, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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