Mesenchymal Stromal Cell (MSC) biology has been studied for more than 4 decades and the cells have been investigated for potential clinical applications for more than 15 years. Progress has become exponential over the past decade due mainly to the broad therapeutic potential of these cells. However, MSC studies have also been subject to controversy and increasing scrutiny as new mechanisms of action are reported and ever-expanding therapeutic applications pursued. In this book, leading authorities from all over the world, who are actively involved in this field, provide state-of-the-art knowledge of the basic biology, translational requirements and latest clinical experience with MSCs. This cutting edge book is the ideal resource for scientists and clinicians interested in pursuing an important and rapidly developing field of research that will eventually help patients and address urgent unmet medical needs. Features include: coverage of the biology of MSCs, latest understanding of mechanisms of action, and role in tissue homeostasis and regeneration; identifying the potential of MSCs in proceeding from bench to bedside from regulatory, GMP production, ethical and safety aspects; and critical analysis of clinical studies and the potential of MSCs to treat a wide variety of human diseases and tissues.

Cellular Therapy for Neurological Injury discusses the current status of cellular therapy for neurological disorders. The primary areas of focus include traumatic brain injury, stroke (ischemic and hemorrhagic), and spinal cord injury. The book explores cell therapy approaches to these and other conditions, while discussing current advances and a literature review in the context of a field that is moving rapidly. The book presents a translational focus, addressing barriers and opportunities to moving forward. The mechanisms of injury are explored, as well as how these mechanisms influence the type of cell therapy used, the route of delivery, and dosing regimen. Written by leaders in the field, this is an invaluable resource for clinicians and researchers alike.

The progression of heart disease is associated with changes in the neurohumoral mechanisms that control cardiac function. The degree to which this neurohumoral remodelling occurs, even before overt signs of cardiac disease become manifest, is important for prognosis. To determine why some patients experience sudden death while others sustain life in the presence of severely compromised cardiac function, the neuronal control of cardiac electrical and mechanical events must be considered. Starting at the level of individual neurons and building upwards, this book describes the synergistic interactions that occur among intrathoracic and CNS feedback loops to permit precise control of regional cardiac behaviour. On this basic science foundation, subsequent clinical chapters explore the remodelling that occurs in this system with ageing, with the evolution of specific cardiac pathologies, and with the psychological concomitants of heart disease. Most importantly, these chapters provide unique insights into how specific therapies like beta-andrenergic receptor blockade not only affect cardiomyocytes directly but also mitigate the adverse neurohumoral changes that accompany disease processes, such as heart failure and essential hypertension. The paradigm advanced in this volume is that heart disease is a multifaceted phenomenon involving the interplay of neurohumoral, cardiomyocyte and structural elements, each of which depends on the other. With our cumulative understanding of these interdependent processes, new avenues for time-appropriate, targeted methods of treating heart diseases can be developed.

Interest in the role of extracellular vesicles (microvesicles and exosomes) is expanding rapidly. It is now apparent that far from being merely cellular debris, these vesicles play a key role in cell-to-cell communication and signaling. Moreover, they are significantly elevated in a number of diseases. This raises the question of their direct role in pathogenesis as well as their possible use as biomarkers.

This book stems from the first international meeting on "Microvesicles and Nanovesicles in Health and Disease" held at Magdalen College, Oxford, in 2010. The purpose of the meeting was to bring together, for the first time, a range of experts from around the world to discuss the latest advances in this field. Key to the study of these vesicles is the availability of methodologies for their measurement in biological fluids. A major section of the meeting focused on a range of exciting new technologies which have been developed for this purpose. The presentations at this meeting form the basis of this book, which will appeal to basic scientists, clinicians, and those developing technology for the measurement of extracellular vesicles.

This book series consists of 3 volumes covering the basic science (Volume 1), clinical science (Volume 2) and the technology and methodology (Volume 3) of autophagy. Volume 1 focuses on the biology of autophagy, including the signaling pathways, regulating processes and biological functions. Autophagy is a fundamental physiological process in eukaryotic cells. It not only regulates normal cellular homeostasis, and organ development and function, but also plays an important role in the pathogenesis of a wide range of human diseases. Thanks to the rapid development of molecular biology and omic technologies, research on autophagy has boomed in recent decades, and more and more cellular and animal models and state-of the-art technologies are being used to shed light on the complexity of signaling networks involved in the autophagic process. Further, its involvement in biological functions and the pathogenesis of various diseases has attracted increased attention around the globe. Presenting cutting-edge knowledge, this book series is a useful reference resource for researchers and clinicians who are working on or interested in autophagy.

Chronic obstructive pulmonary disease (COPD) is the most common respiratory disorder of adults in the developed world and is the fourth main cause of death in the USA. It is also associated with high morbidity, and poses an enormous burden of suffering and expense. Despite this, the disease has received little attention compared with other respiratory conditions such as asthma and lung cancer.
Current treatment can offer some marginal symptomatic relief but does not address the underlying disease process. Indeed, smoking cessation is the only intervention known to alter the rate of disease progression. There is clearly great need, and potential, for the development of superior therapies for symptomatic relief and disease modification. This book brings together leading researchers and physicians to discuss the most recent advances in our understanding of COPD, and draws together basic and clinical aspects relevant to the topic. Coverage includes the basic pathology, current and potential therapies, and detailed consideration of the major theories for the pathogenesis of COPD.

Stellate Cells in Health and Disease is a comprehensive reference providing the most up-to-date knowledge and perspectives on the function of stellate cells affecting the liver and other organs. The text presents comprehensive coverage of their already established role in hepatic fibrosis along with the newer emerging evidence for stellate cell participation in the liver cell (hepatocyte) survival and regeneration, hepatic immunobiology, transplant tolerance, and liver cancer. Chapters describe both animal and human research and the relevance of findings from animal research to human pathophysiology, and also contain sections on future directions which will be of special interest to basic and clinical researchers working on liver fibrosis, hepatic biology, and pathobiology.

This title is intended to assist pharmaceutical scientists in the development of stable protein formulations during the early stages of the product development process, providing a comprehensive review of mechanisms and causes of protein instability in formulation development, coverage of accelerated stability testing methods and relevant analytical methods, and an overview of the drug substance manufacturing process. Preformulation and the development of traditional solutions and lyophilized formulations frequently used for intravenous delivery and non-traditional formulations are also addressed. Because many developments in the field have emerged since the publication of the First Edition, this Second Edition addresses important new patient-friendly developments in the field, such as formulation for implantable devices, needle-free formulation and delivery approaches, and oral delivery of proteins.

Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system (CNS). It affects over 400,000 people in the USA alone and is a common disease world wide. This book will cover a new and emerging field in the development of strategies to treat MS. Until now, the only therapies available for MS treatment have been those directed against inflammation and the immune attack on the CNS. Other treatments are used for symptomatic relief. Remyelination of the CNS has been purely an experimental procedure to date, with many years of research on experimental remyelination in animal models of MS and other myelin disease. As more becomes known about the underlying pathophysiology of MS, it has become apparent that axon loss is a critical component of this primary demyelinating disease and that remyelination of axons at risk, i.e. demyelinated axons, may be the best neuroprotection available. Thus the idea of repairing myelin to both restore conduction to demyelinated fibers, as well as protecting them against future loss, is being seriously explored as a translational therapy. The purpose of this book will be to bring together the experts in the field to discuss what is required to move forward into the clinical application of tissue repair and neuroprotection. The book will begin with a discussion on myelin and the myelinating cell of the CNS and the current state-of-the- art on the cell and molecular biology of the cell, with particular reference toward myelin repair. The book will conclude with a chapter(s) on the clinical application of new myelin repair and axonal protection therapies and the methods by which these new therapies will be evaluated in clinical trials.

The impact of Apoptosis, or programmed cell death, is thought to play a crucial role in the development and progression of disease. Whilst Apoptosis remains extensively studied in the context of immunology, the focus of research has greatly expanded to investigate the key role it is now believed to play in hematopoiesis, angiogenesis, inflammation and organ remodelling. It is hoped that, with an increase in our understanding of the mechanisms controlling apoptosis, there will come the development of a new class of drugs which can pharmacologically manipulate apoptosis and thus provide a means to treat important diseases which currently pose problems to our society.
Containing papers presented at the Eleventh SmithKline Beecham Pharmaceuticals United States Research Symposium and with contributions from leading researchers, Apoptosis in Health and Disease offers a comprehensive review of important developments and research in the field.

It is now more than ten years since Dr. Alec Jeffreys (now Professor Sir Alec Jeffreys, FRS) reported in Nature that the investigation of certain minisatellite regions in the human genome could produce what he termed DNA fingerprints and provide useful information in the fields of paternity testing and forensic analysis. Since that time we have witnessed a revolution in the field of forensic identification. A total change of technology, from serological or electrophoretic analysis of protein polymorphisms to direct investigation of the underlying DNA polymorphisms has occurred in a short space of time. In addition, the evolution and development of the DNA systems themselves has been rapid and spectacular. In the last decade we have progressed from the multilocus DNA fing- prints, through single locus systems based on the same Southern blot RFLP technology, to a host of systems based on the PCR technique. These include Allele Specific Oligonucleotide (ASO)-primed systems detected by dot blots, the "binary" genotypes produced by mapping variations within VNTR repeats demonstrated by minisatellite variant repeat (MVR) analysis, and yet other fragment-length polymorphisms in the form of Short Tandem Repeat (STR) loci. Hand in hand with the increasing range of systems available has been the development of new instrumentation to facilitate their analysis and allow us to explore the possibilities of high volume testing in the form of mass scre- ing and offender databases.

The endothelium, the cell layer that forms the inner lining of blood vessels, is a spatially distributed system that extends to all reaches of the human body. Today, clinical and basic research demonstrates that the endothelium plays a crucial role in mediating homeostasis and is involved in virtually every disease, either as a primary determinant of pathophysiology or as a victim of collateral damage. Indeed, the endothelium has remarkable, though largely untapped, diagnostic and therapeutic potential. This volume endeavors to bridge the bench-to-bedside gap in endothelial biomedicine, with the goal of advancing research and development and improving human health. The book is the first to systematically integrate knowledge about the endothelium from different organ-specific disciplines, including neurology, pulmonary, cardiology, gastroenterology, rheumatology, infectious disease, hematology-oncology, nephrology, and dermatology. Moreover, it is unique in its interdisciplinary approach, drawing on expertise from such diverse fields as evolutionary biology, comparative biology, molecular and cell biology, mathematical modeling and complexity theory, translational research, and clinical medicine.

The relationship between infection and immunity and autophagy, a pathway of cellular homeostasis and stress response, has been a rapidly growing field of study over the last decade. While some cellular processes are pro- or anti-infection, autophagy has been proven to be both: a part of the innate immune response against some microbes, and a cellular pathway subverted by some pathogens to promote their own replication. Autophagy, Infection, and the Immune Response provides a unified overview of the roles of cellular autophagy during microbial infection. Introductory chapters ground the reader by delineating the autophagic pathway from a cellular perspective, and by listing assays available for measuring autophagy. Subsequent chapters address virus interactions with autophagy machinery, the various roles of autophagy parasitic infection, and interactions of bacteria with the autophagic pathway. Concluding chapters explore the relationships of autophagy to systemic immune responses, including antigen presentation, ER stress, and production of IFN-gamma. Designed as a resource for those interested in initiating studies on the relationship between autophagy and infection or immunity, Autophagy, Infection, and the Immune Response combines practical state-of the art technique descriptions with an overview of the wide variety of known interactions between pathogens and the autophagic pathway.

Since its discovery, the mammalian target of rapamycin (mTOR) has been shown to regulate many critical molecular processes in eukaryotes such as metabolism, growth, survival, aging, synaptic plasticity, memory, and immunity. In mTOR: Methods and Protocols expert researchers in the field detail many of the methods which are now commonly used to study mTOR. These include methods and techniques used for the study of the mTOR pathway and potential therapeutic applications of mTOR inhibitors such as, immunosuppressive and anticancer agents. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, mTOR: Methods and Protocols seeks to aid scientists in the further study of this crucially important molecule ranging from the analysis of signal transduction events within a cell to the assessment of complex human diseases such as metabolic disorders or cancer.

"Cellular Physiology of Nerve and Muscle" offers a state of the art introduction to the basic physical, electrical, and chemical principles central to the function of nerve and muscle cells. The text begins with an overview of the origin of electrical membrane potential, then clearly illustrates the cellular physiology of nerve cells and muscle cells. Throughout, this new edition simplifies difficult concepts with accessible models and straightforward descriptions of experimental results.

The fourth edition of Cellular Physiology of Nerve and Muscle features new material including:

- An all-new introduction to electrical signaling in the nervous system
- Expanded coverage of synaptic transmission and synaptic plasticity
- A quantitative overview of the electrical properties of cells
- New detailed illustrations

Transporters are proteins which span the plasma membrane and regulate the traffic of small molecules in and out of the cell. Transporters play a particularly important role in chemical signalling between neurons in the CNS, where they act to control the concentration of neurotransmitters in the synapse. The majority of transporters which are actively being pursued as targets for drug discovery are CNS located and this reflects the history of the field which began with the tricyclic antidepressants (TCAs) over half a century ago. The use of transporter inhibition to regulate the synaptic concentrations of key neurotransmitters is an established approach in the discovery of psychiatric medications. This volume reviews advances in the field of transporters as targets for drug discovery in the last 10 years. The volume will be of interest to scientists engaged in drug research in the pharmaceutical industry, biotech and academia. Following an overview chapter, seven chapters written by leading experts in their area reflect a range of topics pertinent to the transporter field. General topics include recent advances in the structural biology of transporters and its impact on potential structure based drug design and the design of ligands for Positron Emission Tomography and the importance of molecular imaging in understanding early clinical data. Medicinal chemistry approaches are described outlining the discovery of selective serotonin, noradrenaline and dopamine reuptake inhibitors, current efforts towards the discovery of mixed re-uptake inhibitors with varied flavours of monoamine inhibition, advances in the development of inhibitors for the glycine transporter and the discovery of subtype selective EAAT inhibitors. In addition to being an interesting read, the reader will receive a critical overview of progress made in this rapidly developing field."

N-acetylaspartate (NAA), the acetylated form of the amino acid aspartate, is one of the most highly concentrated chemicals in the brains of humans, yet its function remains elusive. NAA is used in nonsurgical analyses of nerve cell dysfunction, and it is implicated in a disorder known as Canavan's disease. This book reviews research from around the world in the study of NAA, and the roles it plays in neuronal development and functioning.

Kruppel-like factors (KLFs) are attracting great attention across a wide spectrum of biological sciences and medicine because of their remarkable biological potency and the diversity of roles they play in the physiological and pathological changes of cells and tissues. This book is a comprehensive compendium of the latest research on the molecular mechanisms of KLFs, describing their roles in transcriptional regulation, cellular differentiation and development, the pathogenesis of the liver and cardiovascular systems and cancer, and generation of ES cells and iPS cells. As the only concise treatise written to date by leading experts in the field, it serves as an authoritative review of this family of molecules and is an essential reference for all who are interested in KLFs. The book also explores the potential of KLFs as targets for novel therapeutics and diagnostics, and will be invaluable in those fields.

Food or calorie restriction has been shown in many short-lived animals and the rhesus monkey to prolong life-span. Life-long nutrition studies are not possible in humans because of their long survival. Studies over two to six years in healthy adult humans have, however, shown that a 20% reduction in food or calorie intake slows many indices of normal and disease-related aging. Thus, it is widely believed that long-term reduction in calorie or food intake will delay the onset of age-related diseases such as heart disease, diabetes and cancer, and so prolong life. Over the last 20 or more years there has been a progressive rise in food intake in many countries of the world, accompanied by a rising incidence of obesity. Thus our increasing food and calorie intake has been linked to the rising incidence of cardiovascular disease and diabetes in early adult life. It is accepted that overeating, accompanied by reduced physical exercise, will lead to more age-related diseases and shortening of life-span. The answer is to reduce our calorie intake, improve our diet, and exercise more. But calorie restriction is extremely difficult to maintain for long periods. How then can we solve this problem? Edited by a team of highly distinguished academics, this book provides the latest information on the beneficial effects of calorie restriction on health and life-span. This book brings us closer to an understanding at the molecular, cellular and whole organism level of the way forward.

Stem cells potentially offer a novel therapeutic platform to treat bone disease. They also help the scientist understand the molecular and cellular aetiology of bone disorders. Gaining knowledge on the nature and application of stem cell sciences is a prerequisite for understanding their potential in treating or preventing bone disorders. Stem Cells and Bone Tissue is designed to address these areas in three sections: Introductory Text and Sources of Stem Cells for Skeletal Tissue Cellular and Molecular Aspects Conditions, Applications, Treatments and Repairs Coverage includes general aspects of stems cells, sources of stems cells, isolation and purification, applications in regeneration, nanoscale topography, myostatin (GDF-8) signalling, c-Jun, Lnk, cell-derived Factor 1/CXCR4, chromatin remodelling, osteoporosis, osteoarthritis, hypophosphatasia, osteopetrosis, osteogenesis, and many other areas of merit too numerous to mention.

The period between 1950 and 1980 were the golden unique insights into how pathological processes affect years of transmission electron microscopy and produced cell organization. a plethora of new information on the structure of cells This information is vital to current work in which that was coupled to and followed by biochemical and the emphasis is on integrating approaches from functional studies. TEM was king and each micrograph proteomics, molecular biology, genetics, genomics, of a new object produced new information that led to molecular imaging and physiology and pathology to novel insights on cell and tissue organization and their understand cell functions and derangements in disease. functions. The quality of data represented by the images In this current era, there is a growing tendency to of cell and tissues had been perfected to a very high level substitut e modern light microscopic techniques for by the great microscopists of that era including Palade, electron microscopy, because it is less technically Porter, Fawcett, Sjostrand, Rhodin and many others. At demanding and is more readily available to researchers- present, the images that we see in leading journals for This atlas reminds us that the information obtained by the most part do not reach the same technical level and electron microscopy is invaluable and has no substitute.

In the past few years nucleic acids technologies have grown into a powerful analytical and also increasingly therapeutic tool. It has been applied not only to the uncovering of gene functions in many organisms, but also to pathogenetic analysis and recently also for the treatment of human diseases. The book discusses in depth the potential of these innovative methods in the broad field of central nervous system and brain tumours particularly. Whereas there is currently no comprehensive overview on potential and challenges of nucleic acids technologies for basic brain tumours and for the clinical management of patients with brain tumours, this book does explicitly cover the many other aspects of the "RNA World" (pathogenic and therapeutic potential of microRNAs, aptamer technology, etc.), too. With this significantly broadened scope as compared to currently existing books it appears to be an urgently needed new publication.

Animals share the challenge of maintaining an internal environment that is restricted to fairly low ranges of temperature, pH, and water content within a well-protected envelope while engaged in continuous exchanges with the environment in terms of gases, liquids, energy, even as movement of body parts and the entire organism itself is necessary for survival. This dynamic spectrum of changes is further amplified during developmental events or more acutely during responses to pernicious environmental factors in due to trauma and disease. In addition, persistent incidents associated with aging can result in irreversible changes to the allostasis that characterizes the living condition.

In the nervous system, a very high metabolic turnover, fragile but steep ionic gradients, and morphological and structural constraints dictated by the necessity for prompt neuronal transmission of electrical impulses and necessary plasticity result in a highly fragile organ system.

Here we address a small sampling of major constituents of neural function at the cellular and molecular level that play important roles in development and aging, two endogenous processes that embody features of allostasis or the dynamic shifts in set points for specific homeostatic mechanisms associated with development and aging.

The opening chapters discuss the major players in the neurotrophic hypothesis, the neurotrophins. These growth factors have been shown to play a significant role during development and in the maintenance of the adult cholinergic system in CNS as well as in the development of the sensory and sympathetic nervous system. That they are also involved in plasticity events associated with memoryand behavior points to the degenerate nature of signaling molecules that archive specificity by acting in concert as part of ensembles of molecules rather than solitary regulators.

It is widely known that oligodendroglia and myelination events are late arrivals in the developmental scheme of the brain and are also prime targets in early development of ischemic insults. Thus, a chapter on oligodendroglia and myelination in development and aging serves to introduce these nonneuronal partners vital to proper neuronal transmission. Molecular participants in stress responses to both acute and chronic stressors are discussed from different perspectives in following chapters with varying degrees of emphasis on injury versus normal aging and neurodegenerative disease.

The study of neural responses to stress of various kinds has led to a realization of the importance of plasticity and the complexity of the mechanism allowing plasticity in the nervous system. The chapters addressing the topic are followed by an introduction to the amyloid hypothesis, and what may be its central character the enzyme held mostly responsible for the generation of beta amyloid. This if followed by a broader discussion of misfolding proteins in the nervous system and its possible interventions to counteract aging-associated deficits.

Limited in scope but offering a broad sampling, these chapters stress the dynamic features of neuronal responses to internal (developmental) cues or the more harmful external events (injury and disease) in a modern perspective.

Initially believed to be inactive molecules, glycans are now considered essential for life, both under normal and pathological conditions.

This volume of the series "Biology of Extracellular Matrix " reviews the most recent findings on the role of glycans in the development of diseases and the possible therapeutic use of this class of molecules. It shows how the interaction of glycans with growth factors, growth factor binding proteins, extracellular proteases, protease inhibitors, chemokines, morphogens, and adhesive proteins regulates inflammation, infection, cancer, atherosclerosis, thrombosis and embryonic stem cell biology. Furthermore, an extensive survey about the structure and pharmacological effects of unique marine glycosaminoglycans is discussed as well as the possibility of using these glycans as therapeutic agents."