Human Ipsc Derived Disease Models For Drug Discovery

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.

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.

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

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.

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.

This book is a printed edition of the Special Issue "iPS Cells for Modelling and Treatment of Human Diseases" that was published in JCM