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https://www.readbyqxmd.com/read/28645005/application-of-stem-cell-derived-neuronal-cells-to-evaluate-neurotoxic-chemotherapy
#1
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
#2
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
#3
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
#4
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/28643254/gene-targeting-in-rabbits-single-step-generation-of-knock-out-rabbits-by-microinjection-of-crispr-cas9-plasmids
#5
Yoshihiro Kawano, Arata Honda
The development of genome editing technology has allowed gene disruptions to be achieved in various animal species and has been beneficial to many mammals. Gene disruption using pluripotent stem cells is difficult to achieve in rabbits, but thanks to advances in genome editing technology, a number of gene disruptions have been conducted. This paper describes a simple and easy method for carrying out gene disruptions in rabbits using CRISPR/Cas9 in which the gene to be disrupted is marked, the presence or absence of off-target candidates is checked, and a plasmid allowing simultaneous expression of Cas9 and sgRNA is constructed...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28643190/mitochondrial-biogenesis-and-neural-differentiation-of-human-ipsc-is-modulated-by-idebenone-in-a-developmental-stage-dependent-manner
#6
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/28642593/transforming-growth-factor-%C3%AE-1-regulates-the-nascent-hematopoietic-stem-cell-niche-by-promoting-gluconeogenesis
#7
C-Y Zhang, H-M Yin, H Wang, D Su, Y Xia, L-F Yan, B Fang, W Liu, Y-M Wang, A-H Gu, Y Zhou
The understanding of hematopoietic stem cell (HSC) emergence is important to generate HSCs from pluripotent precursors. However, integrated signaling network that regulates the niche of nascent HSCs remains unclear. Herein, we uncovered a novel role of TGF-β1 in the metabolic niche of HSC emergence using the tgf-β1b(-/-) zebrafish. Our findings first showed that Tgf-β1 transcripts were enriched in the nascent HSCs. Loss of tgf-β1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. Moreover, tgf-β1b(+) cells were runx1(+) HSCs and underwent an endothelial-to-hematopoietic-transition process...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28641963/modulation-of-the-heart-s-electrical-properties-by-the-anticonvulsant-drug-retigabine
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28638487/current-strategies-and-challenges-for-purification-of-cardiomyocytes-derived-from-human-pluripotent-stem-cells
#12
REVIEW
Kiwon Ban, Seongho Bae, Young-Sup Yoon
Cardiomyocytes (CMs) derived from human pluripotent stem cells (hPSCs) are considered a most promising option for cell-based cardiac repair. Hence, various protocols have been developed for differentiating hPSCs into CMs. Despite remarkable improvement in the generation of hPSC-CMs, without purification, these protocols can only generate mixed cell populations including undifferentiated hPSCs or non-CMs, which may elicit adverse outcomes. Therefore, one of the major challenges for clinical use of hPSC-CMs is the development of efficient isolation techniques that allow enrichment of hPSC-CMs...
2017: Theranostics
https://www.readbyqxmd.com/read/28638147/sensitivity-of-human-pluripotent-stem-cells-to-insulin-precipitation-induced-by-peristaltic-pump-based-medium-circulation-considerations-on-process-development
#13
Diana Massai, Emiliano Bolesani, Diana Robles Diaz, Christina Kropp, Henning Kempf, Caroline Halloin, Ulrich Martin, Tudor Braniste, Giuseppe Isu, Vanessa Harms, Umberto Morbiducci, Gerald Dräger, Robert Zweigerdt
Controlled large-scale production of human pluripotent stem cells (hPSCs) is indispensable for their envisioned clinical translation. Aiming at advanced process development in suspension culture, the sensitivity of hPSC media to continuous peristaltic pump-based circulation, a well-established technology extensively used in hydraulically-driven bioreactors, was investigated. Unexpectedly, conditioning of low protein media (i.e. E8 and TeSR-E8) in a peristaltic pump circuit induced severe viability loss of hPSCs cultured as aggregates in suspension...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637969/development-of-a-patient-derived-induced-pluripotent-stem-cell-model-for-the-investigation-of-scn5a-d1275n-related-cardiac-sodium-channelopathy
#14
Mamoru Hayano, Takeru Makiyama, Tsukasa Kamakura, Hiroshi Watanabe, Kenichi Sasaki, Shunsuke Funakoshi, Yimin Wuriyanghai, Suguru Nishiuchi, Takeshi Harita, Yuta Yamamoto, Hirohiko Kohjitani, Sayako Hirose, Fumika Yokoi, Jiarong Chen, Osamu Baba, Takahiro Horie, Kazuhisa Chonabayashi, Seiko Ohno, Futoshi Toyoda, Yoshinori Yoshida, Koh Ono, Minoru Horie, Takeshi Kimura
BACKGROUND: TheSCN5Agene encodes the α subunit of the cardiac voltage-gated sodium channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated with reduced NaV1.5 function, including cardiac conduction disease and dilated cardiomyopathy. Curiously, the reported biophysical properties ofSCN5A-D1275N channels vary with experimental system.Methods and Results:First, using a human embryonic kidney (HEK) 293 cell-based heterologous expression system, theSCN5A-D1275N channels showed similar maximum sodium conductance but a significantly depolarizing shift of activation gate (+10 mV) compared to wild type...
June 20, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28637827/islet-encapsulation-physiological-possibilities-and-limitations
#15
Olle Korsgren
A logical cure for type 1 diabetes (T1D) involves replacing the lost insulin-producing cells with new ones, preferably cells from a well-characterized and unlimited source of human insulin-producing cells. This straightforward and simple solution to provide a cure for T1D is immensely attractive but entails at least two inherent and thus far unresolved hurdles: 1) provision of an unlimited source of functional human insulin-producing cells and 2) prevention of rejection without the side effects of systemic immunosuppression...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28637620/runx1-deficiency-familial-platelet-disorder-with-predisposition-to-myeloid-leukemia-fpdmm
#16
REVIEW
Brigitte Schlegelberger, Paula G Heller
In this review, we discuss disease-causing alterations of RUNT-related transcription factor 1 (RUNX1), a master regulator of hematopoietic differentiation. Familial platelet disorder with predisposition to myeloid leukemia (FPDMM) typically presents with (1) mild to moderate thrombocytopenia with normal-sized platelets; (2) functional platelets defects leading to prolonged bleeding; and (3) an increased risk to develop myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), or T-cell acute lymphoblastic leukemia (T-ALL)...
April 2017: Seminars in Hematology
https://www.readbyqxmd.com/read/28637492/expression-patterns-of-fshd-causing-dux4-and-myogenic-transcription-factors-pax3-and-pax7-are-spatially-distinct-in-differentiating-human-stem-cell-cultures
#17
Premi Haynes, Kelly Kernan, Suk-Lin Zhou, Daniel G Miller
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is most commonly inherited in an autosomal dominant pattern and caused by the abnormal expression of DUX4 in skeletal muscle. The DUX4 transcription factor has DNA binding domains similar to several paired class homeotic transcription factors, but only myogenic factors PAX3 and PAX7 rescue cell viability when co-expressed with DUX4 in mouse myoblasts. This observation suggests competition for DNA binding sites in satellite cells might limit muscle repair and may be one aspect of DUX4-associated myotoxicity...
June 21, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28637404/role-of-dna-and-rna-n6-adenine-methylation-in-regulating-stem-cell-fate
#18
Yunshu Wu, Chenchen Zhou, Quan Yuan
Epigenetic modifications have been evidenced to participate in eukaryotic stem cell fate decision. Among the most studied, 5-methylcytosine (m5C) and its derivatives are well-established epigenetic codes that play important roles in stem cell pluripotency and differentiation. Based on improved detection techniques, recent studies have succeeded in defining N6-adenine methylation (m6A) in eukaryotic DNA and RNA. The abundant m6A methylation in RNA was shown to be involved in multiple cellular metabolisms while the presence and functional potential of DNA m6A methylation in different species advanced our knowledge in the m6A-mediated biological processes...
June 21, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28637335/astrocyte-produced-mir-146a-as-a-mediator-of-motor-neuron-loss-in-spinal-muscular-atrophy
#19
Samantha L Sison, Teresa N Patitucci, Emily R Seminary, Eric Villalon, Christian L Lorson, Allison D Ebert
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, is caused by loss of the survival motor neuron-1 (SMN1) gene, which leads to motor neuron loss, muscle atrophy, respiratory distress, and death. Motor neurons exhibit the most profound loss, but the mechanisms underlying disease pathogenesis are not fully understood. Recent evidence suggests that motor neuron extrinsic influences, such as those arising from astrocytes, contribute to motor neuron malfunction and loss. Here we investigated both loss-of-function and toxic gain-of-function astrocyte mechanisms that could play a role in SMA pathology...
June 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28636920/nanog-fluctuations-in-embryonic-stem-cells-highlight-the-problem-of-measurement-in-cell-biology
#20
Rosanna C G Smith, Patrick S Stumpf, Sonya J Ridden, Aaron Sim, Sarah Filippi, Heather A Harrington, Ben D MacArthur
A number of important pluripotency regulators, including the transcription factor Nanog, are observed to fluctuate stochastically in individual embryonic stem cells. By transiently priming cells for commitment to different lineages, these fluctuations are thought to be important to the maintenance of, and exit from, pluripotency. However, because temporal changes in intracellular protein abundances cannot be measured directly in live cells, fluctuations are typically assessed using genetically engineered reporter cell lines that produce a fluorescent signal as a proxy for protein expression...
June 20, 2017: Biophysical Journal
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