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Author: Mike Clements
Publisher: Methods in Pharmacology and To
ISBN: 9781493982646
Category : Medical
Languages : en
Pages : 356
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Book Description
Author: Mike Clements
Publisher: Methods in Pharmacology and To
ISBN: 9781493982646
Category : Medical
Languages : en
Pages : 356
Get Book Here
Book Description
Author: Saura C. Sahu
Publisher: John Wiley & Sons
ISBN: 1119135435
Category : Science
Languages : en
Pages : 1010
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Book Description
A comprehensive and authoritative compilation of up-to-date developments in stem cell research and its use in toxicology and medicine Presented by internationally recognized investigators in this exciting field of scientific research Provides an insight into the current trends and future directions of research in this rapidly developing new field A valuable and excellent source of authoritative and up-to-date information for researchers, toxicologists, drug industry, risk assessors and regulators in academia, industry and government
Author: Benjamin Arthur Llewellyn Finnin
Publisher:
ISBN:
Category :
Languages : en
Pages : 412
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Book Description
Drug discovery and development requires preclinical models to eliminate flawed compounds from development pipelines. Unfortunately, current models have limitations, occasionally resulting in toxic or ineffective compounds progressing to the clinic at great cost and patient risk. Utilising stem cell technology, it is now possible to generate sophisticated models with human biology and physiological context, potentially overcoming the limitations of more established preclinical models. In this thesis I have investigated the use of embryonic stem cell derived cardiac cells for use as models in pharmacology, physiology and toxicology studies. Mouse embryonic stem cells were differentiated to generate cardiomyocytes in multicellular aggregates containing not only myocytes, but also pacemaker cells, fibroblasts and endothelium. These aggregates were used for pharmacology studies, where the signaling resulting from [beta]-adrenoceptor and adenosine receptor stimulation was explored. Using the same differentiation method, in combination with a pan-cardiac reporter for cell enrichment, the function of individual cardiac cells was measured using calcium imaging. Following extensive method development, multiple phenotypes were identified in the enriched population based on spontaneous calcium oscillations. These distinct phenotypes were characterised based on calcium oscillation kinetics, pharmacology and immunocytochemistry. Using human stem cell derived cardiomyocyte aggregates I studied the effects of doxorubicin (a known cardio-toxin) and Trastuzumab, a humanised antibody with disputed cardio-toxicity. Following extensive method development, toxicity was observed for both doxorubicin and Trastuzumab. Furthermore, mechanistic studies implicate multiple cell types mediating Trastuzumab toxicity via a complicated signaling pathway. Based on my results, as models of pharmacology stem cell derived cardiomyocytes provide access to a physiologically heterogeneous model that may be useful for the screening of compounds for non-specific cardiac activity. Unfortunately, the complexity of multicellular aggregates limits their use in characterizing less established, or complicated receptor signaling pathways. Results from calcium imaging studies indicate that at a single cell level, there is considerable heterogeneity of stem cell derived cardiac cells. Focusing on cells with spontaneous calcium oscillations, presumably pacemaker cells, it may be possible to gain greater insight into the mechanisms required to maintain spontaneous cardiac activity, and identify drugs that disrupt it. The results of the Trastuzumab toxicity study provide evidence of a novel mechanism of Trastuzumab cardio-toxicity. More importantly, these results support the use of stem cell derived models for toxicology screening, particularly of humanised antibodies whose toxicity may be missed in classical models. The work presented in this thesis identified novel pacemaker phenotypes previously unreported, and a novel mechanism for Trastuzumab toxicity. Furthermore, this thesis highlights the strengths and weaknesses of stem cell derived models for use in pharmacology, physiology and toxicology assays.
Author: James L Sherley
Publisher: Royal Society of Chemistry
ISBN: 178262421X
Category : Medical
Languages : en
Pages : 316
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Book Description
Toxicity against tissue stem cells (TSCs) is a major problem in drug development and environmental health science. Despite their essential function in all human cellular tissues, the nature of tissue stem cells is not fully understood. The small fraction of stem cells in tissues and the lack of specific biomarkers for their quantification present a formidable challenge to developing tools for their study and assays that can identify stem cell-toxic agents. Human Stem Cell Toxicology reveals TSC toxicity as a biomedical reality that is now well under siege by newly emerging ideas and technologies, despite these challenges. Chapters consider stem cell toxicity by environmental agents, pharmaceutical drug candidates, and marketed therapeutic medicines with adverse side effects. New insights to cellular, molecular, biochemical and chemical mechanisms of human tissue stem cell toxicity are brought together. Experimental and theoretical treatments are of specific topics, including approaches to monitoring TSC function, newly discovered TSC types and TSC toxicity resistance mechanisms are covered by expert authors. This book informs and champions the continued development of innovative technologies to predict the TSC toxicity of compounds before their use, whether in patients or the environment, by addressing emerging new cell-based approaches and concepts for technical innovation. This publication will be a useful reference for postgraduate students and researchers working in toxicology, pharmaceutical science, tissue cell biology and stem cell biology.
Author: Theodore P. Rasmussen
Publisher: John Wiley & Sons
ISBN: 1119283221
Category : Science
Languages : en
Pages : 388
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Book Description
This book contains material contributed by forward-looking scientists who work at the interface of stem cell research and applied science with the aim to improve human fetal safety and the understanding of human developmental and degenerative disorders. Provides important platforms and contemporary accounts of the state of stem cell research in the fields of toxicology and teratology Considers both in vitro uses of stem cells as platforms for teratology and also stem cellopathies, which are in vivo developmental and degenerative disorders Helps the pharmaceutical industry and safety and environmental authorities validate the status quo of in vitro toxicity test systems based on human pluripotent stem cells and their derivatives
Author: Minoru Tomizawa
Publisher: BoD – Books on Demand
ISBN: 9535124714
Category : Science
Languages : en
Pages : 534
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Book Description
Pluripotent stem cells have distinct characteristics: self-renewal and the potential to differentiate into various somatic cells. In recent years, substantial advances have been made from basic science to clinical applications. The vast amount knowledge available makes obtaining concise yet sufficient information difficult, hence the purpose of this book. In this book, embryonic stem cells, induced pluripotent stem cells, and mesenchymal stem cells are discussed. The book is divided into five sections: pluripotency, culture methods, toxicology, disease models, and regenerative medicine. The topics covered range from new concepts to current technologies. Readers are expected to gain useful information from expert contributors.
Author: C. K. Atterwill
Publisher: Cambridge University Press
ISBN: 9780521326841
Category : Medical
Languages : en
Pages : 490
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Book Description
The volume brings together the once disparate knowledge of cultural techniques and thus provides an important reference work for industrial and academic toxicologists.
Author:
Publisher: Elsevier
ISBN: 0443132542
Category : Psychology
Languages : en
Pages : 272
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Book Description
Stem Cells in Neurotoxicology, Volume Twelve in the Advances in Neurotoxicology series, presents interesting chapters written by an international board of authors. Chapters in this new release include Brain organoids as a translational model of human developmental neurotoxicity, Self-organizing human neuronal cultures in the modeling of environmental impacts on learning and intelligence, Utilization of human stem cell/neural progenitor tests to examine neurotoxic impacts on differentiation, Characterization of neuronal and other cellular sub-types in human stem cell cortical neuron differentiations, Utility of human stem cell models to study persistent neurotoxicity, and Utility of human stem cell models to study chronic neurotoxicity.
Author: Arlene Chiu
Publisher: Springer Science & Business Media
ISBN:
Category : Science
Languages : en
Pages : 488
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Book Description
A discussion of all the key issues in the use of human pluripotent stem cells for treating degenerative diseases or for replacing tissues lost from trauma. On the practical side, the topics range from the problems of deriving human embryonic stem cells and driving their differentiation along specific lineages, regulating their development into mature cells, and bringing stem cell therapy to clinical trials. Regulatory issues are addressed in discussions of the ethical debate surrounding the derivation of human embryonic stem cells and the current policies governing their use in the United States and abroad, including the rules and conditions regulating federal funding and questions of intellectual property.
Author: Deepak A. Lamba
Publisher: CRC Press
ISBN: 1315402173
Category : Medical
Languages : en
Pages : 279
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Book Description
One of the biggest challenges faced in medical research had been to create accurate and relevant models of human disease. A number of good animal models have been developed to understand the pathophysiology. However, not all of them reflect the human disorder, a classic case being Usher’s syndrome where the mutant mice do not have the same visual and auditory defects that patients face. There are others which have been even more difficult to model due to the multi-factorial nature of the condition and due to lack of discovery of a single causative gene such as age-related macular degeneration or Alzheimer’s syndrome. Thus a more relevant and accurate system will allow us to make better predictions on relevant therapeutic approaches. The discovery of human pluripotent stem cells in 1998 followed by the technological advances to reprogram somatic cells to pluripotent-stem cell-like cells in 2006 has completely revolutionized the way we can now think about modelling human development and disease. This now coupled with genome editing technologies such as TALENS and CRISPRs have now set us up to develop in vitro models both 2D as well as 3D organoids, which can more precisely reflect the disease in the patients. These combinatorial technologies are already providing us with better tools and therapeutics in drug discovery or gene therapy. This book summarizes both the technological advances in the field of generation of patient specific lines as well as various gene editing approaches followed by its applicability in various systems. The book will serve as a reference for the current state of the field as it: -Provides a comprehensive overview of the status of the field of patients derived induced pluripotent stem cells. -Describes the use of cardiac cells as a main featured component within the book. -Examines drug toxicity analysis as a working example throughout the book.
