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Human Ipsc Derived Disease Models For Drug Discovery
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Book Synopsis Human iPSC-derived Disease Models for Drug Discovery by : Markus H. Kuehn
Download or read book Human iPSC-derived Disease Models for Drug Discovery written by Markus H. Kuehn and published by Springer Nature. This book was released on 2023-11-23 with total page 331 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since their development a decade ago, human induced pluripotent stem cells (iPSC) have revolutionized the study of human disease, given rise to regenerative medicine technologies, and provided exceptional opportunities for pharmacologic research. These cells provide an essentially unlimited supply of cell types that are difficult to obtain from patients, such as neurons or cardiomyocytes, or are difficult to maintain in primary cell culture. iPSC can be obtained from patients afflicted with a particular disease but, in combination with recently developed gene editing techniques, can also be modified to generate disease models. Moreover, the new techniques of 3 Dimensional printing and materials science facilitate the generation of organoids that can mirror organs under disease conditions. These properties make iPSC powerful tools to study how diseases develop and how they may be treated. In addition, iPSC can also be used to treat conditions in which the target cell population has been lost and such regenerative approaches hold great promise for currently untreatable diseases, including cardiac failure or photoreceptor degenerations.
Book Synopsis Novel Biomaterials for Regenerative Medicine by : Heung Jae Chun
Download or read book Novel Biomaterials for Regenerative Medicine written by Heung Jae Chun and published by Springer. This book was released on 2018-10-24 with total page 533 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book explores in depth a wide range of new biomaterials that hold great promise for applications in regenerative medicine. The opening two sections are devoted to biomaterials designed to direct stem cell fate and regulate signaling pathways. Diverse novel functional biomaterials, including injectable nanocomposite hydrogels, electrosprayed nanoparticles, and waterborne polyurethane-based materials, are then discussed. The fourth section focuses on inorganic biomaterials, such as nanobioceramics, hydroxyapatite, and titanium dioxide. Finally, up-to-date information is provided on a wide range of smart natural biomaterials, ranging from silk fibroin-based scaffolds and collagen type I to chitosan, mussel-inspired biomaterials, and natural polymeric scaffolds. This is one of two books to be based on contributions from leading experts that were delivered at the 2018 Asia University Symposium on Biomedical Engineering in Seoul, Korea – the companion book examines in depth the latest enabling technologies for regenerative medicine.
Book Synopsis Medical Applications of iPS Cells by : Haruhisa Inoue
Download or read book Medical Applications of iPS Cells written by Haruhisa Inoue and published by Springer. This book was released on 2019-04-01 with total page 190 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume highlights recent advances using iPS cells in disease modeling and medical applications along with new technologies that enhance the power of iPS cells. While the discovery of iPS cells has provided excellent opportunities for developing models of human diseases, platforms for drug discovery and cell therapies, iPS cell technology still faces many challenges. Presenting the latest advances in this rapidly evolving research area, this book is intended to widen the community of researchers and clinicians interested in the exciting field of iPS cells.
Book Synopsis Phenotyping of Human iPSC-derived Neurons by : Elizabeth D. Buttermore
Download or read book Phenotyping of Human iPSC-derived Neurons written by Elizabeth D. Buttermore and published by Academic Press. This book was released on 2022-09-09 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: Phenotyping of Human iPSC-derived Neurons: Patient-Driven Research examines the steps in a preclinical pipeline that utilizes iPSC-derived neuronal technology to better understand neurological disorders and identify novel therapeutics, also providing considerations and best practices. By presenting example projects that identify phenotypes and mechanisms relevant to autism spectrum disorder and epilepsy, this book allows readers to understand what considerations are important to assess at the start of project design. Sections address reproducibility issues and advances in technology at each stage of the pipeline and provide suggestions for improvement. From patient sample collection and proper controls to neuronal differentiation, phenotyping, screening, and considerations for moving to the clinic, these detailed descriptions of each stage of the pipeline will help everyone, regardless of stage in the pipeline. In recent years, drug discovery in the neurosciences has struggled to identify novel therapeutics for patients with varying indications, including epilepsy, chronic pain, and psychosis. Current treatment options for such patients are decades old and offer little relief with many side effects. One explanation for this lull in novel therapeutics is a lack of novel target identification for neurological disorders (and target identification requires exemplar preclinical data). To improve on the preclinical work that often relies on rodent modeling, the field has begun utilizing patient-derived induced pluripotent stem cells (iPSCs) to differentiate neurons in vitro for preclinical characterization of neurological disease and target identification. Discusses techniques and new technology for iPSC culturing and neuronal differentiation to establish best practices in the lab Outlines considerations for phenotypic assay development Provides information about the successes, failures, and implications of phenotyping and screening with iPSC-derived neurons Describes how human iPSC-derived neurons are being used for preclinical discovery research as well as the development of therapeutics utilizing hiPSC-derived neurons
Book Synopsis Pluripotent Stem Cells by : Uma Lakshmipathy
Download or read book Pluripotent Stem Cells written by Uma Lakshmipathy and published by Humana Press. This book was released on 2013-04-02 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human pluripotent stem cells such as human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) with their unique developmental plasticity hold immense potential as cellular models for drug discovery and in regenerative medicine as a source for cell replacement. While hESC are derived from a developing embryo, iPSC are generated with forced expression of key transcription factors to convert adult somatic cells to ESC-like cells, a process termed reprogramming. Using iPSC overcomes ethical issues concerning the use of developing embryos and it can be generated from patient-specific or disease-specific cells for downstream applications. Pluripotent Stem Cells: Methods and Protocols highlights the best methods and systems for the entire work flow. Divided into four convenient sections, topics include a focus on producing iPSC from diverse somatic sources, media systems for expanding ESC and iPSC with detailed protocols for directed differentiation into specific lineages, commonly used cellular and molecular characterization methods , and the potential application of labeled stem cells with specific methods for cloning, gene delivery and cell engineering. Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Pluripotent Stem Cells: Methods and Protocols seeks to serve both professionals and novices with its well-honed methodologies in an effort to further our knowledge of this essential cellular feature.
Book Synopsis Human iPS Cells in Disease Modelling by : Keiichi Fukuda
Download or read book Human iPS Cells in Disease Modelling written by Keiichi Fukuda and published by Springer. This book was released on 2016-03-30 with total page 102 pages. Available in PDF, EPUB and Kindle. Book excerpt: Human iPS cells have a great potential to be cell sources for regenerative medicine because of the promise of infinite self-renewal and the capability to differentiate into multiple cell types. This book focuses on another great potential of human iPS cells, which is the establishment of human disease models using patient-specific iPS cells. Human iPS cells can be easily obtained from a patient’s somatic cells and provide the entire information on the patient’s genome. Accordingly, we can generate disease models for inheritable diseases in cell culture dishes using iPS cells. This is a quite new technique but holds tremendous potential for our increased understanding of pathogenesis, and will then be the basis for novel drug development industries. All the authors are leading researchers in this field and they have reported many kinds of patient-derived iPS cells. In this book, they introduce the aspects that could be recapitulated in terms of disease modelling as well as further innovative findings such as novel pathogenetic insights and novel therapies.
Book Synopsis Development of in Vitro Drug Screening Platforms Using Human Induced Pluripotent Stem Cell-derived Cardiovascular Cells by : Yosuke Kurokawa
Download or read book Development of in Vitro Drug Screening Platforms Using Human Induced Pluripotent Stem Cell-derived Cardiovascular Cells written by Yosuke Kurokawa and published by . This book was released on 2017 with total page 117 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug-induced cardiotoxicity is a critical challenge in the development of new drugs. Since the advent of human pluripotent stem cell-derived cardiomyocytes (CMs), researchers have explored ways to utilize these cells for in vitro preclinical drug screening applications. One area of interest is microphysiological systems (i.e. organ-on-a-chip), which aims to create more complex in vitro models of human organ systems, thus improving drug response predictions. In this dissertation, we investigated novel analysis methods and model platforms for detecting drug-induced cardiotoxicity using human induced pluripotent stem cell (iPSC)-derived cardiovascular cells. First, we utilized human iPSC-derived CMs (iPS-CMs) to establish optical methods of detecting cardioactive compounds. We utilized optical flow to assess the iPS-CM contractions captured using brightfield microscopy. The parameters were then analyzed using a machine learning algorithm to determine the accuracy of detection that can be obtained by the model for a given drug concentration. This result was compared to the analysis of the calcium transients measured using a genetically encoded calcium indicator (GCaMP6). The brightfield contraction analysis matched the detection sensitivity of fluorescent calcium transient analysis, while also being able to detect the effects of excitation-contraction decoupler (blebbistatin), which was not detected using calcium transient analysis. Second, we utilize iPS-CMs to model trastuzumab-related cardiotoxicity. Trastuzumab, a monoclonal antibody against ErbB2 (Her2), is used to treat Her2+ breast cancer and has known clinical cardiotoxicity. We demonstrated that an active ErbB2 signaling via binding of neuregulin-1 (NRG-1) to ErbB4 is necessary to detect the cardiotoxic effects of trastuzumab. Activation of ErbB2/4 pathway via NRG-1 is cardioprotective, and we also demonstrated that heparin-binding epidermal growth factor-like growth factor (HB-EGF) similarly activates the ErbB2/4 pathway. Finally, we established a co-culture platform of iPS-CMs and endothelial cells (ECs), which recapitulated the physiological phenomenon of EC-secreted NRG-1 activating the ErbB2/4 pathway on the CMs. Third, we demonstrated the use of human iPSC-derived ECs (iPS-ECs) for creating 3-dimensionial vascular networks inside microfluidic devices. The iPS-ECs were characterized for EC markers and physiological functions. We utilized a CDH5-mCherry iPSC line to create iPS-ECs that expressed VE-cadherin fused to mCherry. The vascular networks formed by the iPS-ECs were patent and perfusable, retaining 70 kDa dextran within the lumen of the vessels. The vasculature responded to small molecule inhibitors, showing increased vessel formation in response to TGF-[beta] inhibitor SB431542 and decreased vessel formation in response to multi-targeted receptor tyrosine kinase inhibitor sunitinib. Taken together, our findings advance the current understanding and utility of iPS-CMs for drug screening applications, while establishing platforms for creating microphysiological systems that incorporate iPS-EC co-culture. The use of iPSC-derived cells opens possibilities for disease-specific and patient-specific drug screening applications in the future.
Book Synopsis Novel Concepts in iPSC Disease Modeling by : Alexander Birbrair
Download or read book Novel Concepts in iPSC Disease Modeling written by Alexander Birbrair and published by Academic Press. This book was released on 2022-01-08 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: The series Advances in Stem Cell Biology is a timely and expansive collection of comprehensive information and new discoveries in the field of stem cell biology. iPSCs - Novel Concepts, Volume 15 addresses how important induced pluripotent stems cells are and how can they can help treat certain diseases. Somatic cells can be reprogrammed into induced pluripotent stem cells by the expression of specific transcription factors. These cells have been transforming biomedical research over the last 15 years. This volume will address the advances in research of how induced pluripotent stem cells are being used for treatment of different disorders, such as liver disease, type-1 diabetes, Parkinson’s disease, macular degeneration of the retina and much more. The volume is written for researchers and scientists in stem cell therapy, cell biology, regenerative medicine and organ transplantation; and is contributed by world-renowned authors in the field. Provides overview of the fast-moving field of stem cell biology and function, regenerative medicine and therapeutics Covers spinal cord injuries, type-1 diabetes, liver disease, Parkinson’s disease, graft vs. host disease, and much more Contributed by world-renown experts in the field
Book Synopsis Pluripotent Stem Cells by : Minoru Tomizawa
Download or read book Pluripotent Stem Cells written by Minoru Tomizawa and published by BoD – Books on Demand. This book was released on 2016-07-20 with total page 534 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis Improving and Accelerating Therapeutic Development for Nervous System Disorders by : Institute of Medicine
Download or read book Improving and Accelerating Therapeutic Development for Nervous System Disorders written by Institute of Medicine and published by National Academies Press. This book was released on 2014-02-06 with total page 107 pages. Available in PDF, EPUB and Kindle. Book excerpt: Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.
Book Synopsis Human Embryonic Stem Cells by : Arlene Chiu
Download or read book Human Embryonic Stem Cells written by Arlene Chiu and published by Springer Science & Business Media. This book was released on 2003-08 with total page 488 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Book Synopsis Patient-Specific Stem Cells by : Deepak A. Lamba
Download or read book Patient-Specific Stem Cells written by Deepak A. Lamba and published by CRC Press. This book was released on 2017-04-07 with total page 279 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Dynamic-Clamp written by Alain Destexhe and published by Springer Science & Business Media. This book was released on 2009-03-11 with total page 428 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dynamic-clamp is a fascinating electrophysiology technique that consists of merging living neurons with computational models. The dynamic-clamp (also called “conductance injection”) allows experimentalists and theoreticians to challenge neurons (or any other type of cell) with complex conductance stimuli generated by a computer. The technique can be implemented from neural simulation environments and a variety of custom-made or commercial systems. The real-time interaction between the computer and cell also enables the design of recording paradigms with unprecedented accuracy via a computational model of the electrode. Dynamic-Clamp: From Principles to Applications contains contributions from leading researchers in the field, who investigate these paradigms at the cellular or network level, in vivo and in vitro, and in different brain regions and cardiac cells. Topics discussed include the addition of artificially-generated synaptic activity to neurons; adding, amplifying or neutralizing voltage-dependent conductances; creating hybrid networks with real and artificial cells; attaching simulated dendritic tree structures to the living cell; and connecting different neurons. This book will be of interest to experimental biophysicists, neurophysiologists, and cardiac physiologists, as well as theoreticians, engineers, and computational neuroscientists. Graduate and undergraduate students will also find up-to-date coverage of physiological problems and how they are investigated.
Book Synopsis Mitochondrial Disorders in Neurology by : Anthony Henry Vernon Schapira
Download or read book Mitochondrial Disorders in Neurology written by Anthony Henry Vernon Schapira and published by Butterworth-Heinemann. This book was released on 1994 with total page 272 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondrial Disorders in Neurology provides an overview of mitochondrial diseases. This book discusses the effects of mitochondrial dysfunction based on the relevant biochemistry and molecular genetics. The abnormal muscle and mitochondrial morphology in a variety of clinical presentations from isolated ophthalmoplegia to severe encephalopathy are also elaborated. This text likewise deliberates Leber's hereditary optic neuropathy, neurodegenerative disorders, and respiratory chain defects. Other topics covered include mitochondrial DNA and the genetics of mitochondrial disease; cytochrome ox ...
Book Synopsis Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders by : Adeboye Adejare
Download or read book Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders written by Adeboye Adejare and published by Academic Press. This book was released on 2016-09-20 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders: Alzheimer’s Disease examines the drug discovery process for neurodegenerative diseases by focusing specifically on Alzheimer’s Disease and illustrating the paradigm necessary to ensure future research and treatment success. The book explores diagnosis, epidemiology, drug discovery strategies, current therapeutics, and much more to provide a holistic approach to the discovery, development, and treatment of Alzheimer’s Disease. Through its coverage of the latest research in targeted drug design, preclinical studies, and mouse and rat models, the book is a must-have resource for all pharmaceutical scientists, pharmacologists, neuroscientists, and clinical researchers working in this area. It illustrates why these drugs tend to fail at the clinical stage, and examines Alzheimer’s Disease within the overall context of improving the drug discovery process for the treatment of other neurodegenerative disorders. Provides a compilation of chemical considerations required in drug discovery for the treatment of neurodegenerative disorders Examines different classes of compounds currently being used in discovery and development stages Explores in vitro and in vivo models with respect to their ability to translate these models to human conditions Distills the most significant information across multiple areas of Alzheimer’s disease research to provide a single, comprehensive, and balanced resource
Book Synopsis Recent Advances in iPSC Disease Modeling, Volume 1 by : ALEXANDER BIRBRAIR
Download or read book Recent Advances in iPSC Disease Modeling, Volume 1 written by ALEXANDER BIRBRAIR and published by Academic Press. This book was released on 2020-07-30 with total page 320 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent Advances in iPSC Disease Modeling, Volume 1 addresses how induced pluripotent stem cells can be used to model various diseases. Somatic cells are reprogrammed into induced pluripotent stem cells by the expression of specific transcription factors. These cells are transforming biomedical research in the last 15 years. This volume teaches readers about current advances in the field. This book describes the use of induced pluripotent stem cells to model several diseases in vitro, enabling us to study the cellular and molecular mechanisms involved in different pathologies. Further insights into these mechanisms will have important implications for our understanding of disease appearance, development, and progression. In recent years, remarkable progress has been made in the obtention of induced pluripotent stem cells and their differentiation into several cell types, tissues, and organs using state-of-art techniques. These advantages facilitated identification of key targets and definition of the molecular basis of several disorders. The volume is written for researchers and scientists in stem cell therapy, cell biology, regenerative medicine and organ transplantation; and is contributed by world-renowned authors in the field. Provides overview of the fast-moving field of induced pluripotent stem cell technology, regenerative medicine, and therapeutics Covers the following diseases: severe congenital neutropenia, sickle cell and Diamond-Blackfan anemias, muscular dystrophies, Bernard-Soulier syndrome, familial hypercholesterolemia type II A, Werner syndrome, lysosomal storage diseases, and more Contains description of cutting-edge research on the development of disease-specific human pluripotent stem cells. These cells allow us to study cellular and molecular processes involved in several human diseases
Book Synopsis Tissue Engineering by : Chandra P. Sharma
Download or read book Tissue Engineering written by Chandra P. Sharma and published by Academic Press. This book was released on 2022-01-25 with total page 724 pages. Available in PDF, EPUB and Kindle. Book excerpt: Tissue Engineering: Current Status and Challenges bridges the gap between biomedical scientists and clinical practitioners. The work reviews the history of tissue engineering, covers the basics required for the beginner, and inspires those in the field toward future research and application emerging in this fast-moving field. Written by global experts in the field for those studying and researching tissue engineering, the book reviews regenerative technologies, stem cell research and regeneration of organs. It then moves to soft tissue engineering (heart, vascular, muscle and 3D scaffolding and printing), hard tissue engineering (bone, dental myocardial and musculoskeletal) and translational avenues in the field. Introduces readers to the history and benefits of tissue engineering Includes coverage of new techniques and technologies, such as nanotechnology and nanoengineering Presents concepts, ideology and theories which form the foundation for next-generation tissue engineering
