Stem Cell Based Therapy For Lung Disease

This book presents state-of-the-art pre-clinical models and clinical applications of stem-cell-based therapies applied to different lung diseases, with a special focus on the translation of bench data into clinical studies. Starting with the assumption that abnormal lung tissue repair and regeneration has emerged as the driving force underlying pathogenesis and progression in many lung diseases, it sheds new light on the potential of stem/stromal cells as drivers of repair and sources of reparative factors in the lung. The first part of the book offers an overview of stem cell types and mechanisms involved in lung development, homeostasis, repair and regeneration, and reveals the crucial role of the extracellular matrix within the lung microenvironment. In the second part, leading experts present the latest pre-clinical evidence and clinical applications of stem-cell-based therapies in a wide variety of lung diseases, ranging from COPD and lung fibrosis to other rare lung diseases. The last section discusses stem cell delivery systems and devices, such as aerosolised spray application. This book appeals to pneumologists, stem cell and matrix biologists, as well as bioengeneers with a special interest in regenerative medicine applied to pulmonary diseases.

This book presents a comprehensive overview of the current understanding of the organization of endogenous lung stem and progenitor cell compartments during fetal lung development, postnatal lung growth and in adulthood. Progressing stage by stage, the chapters on fetal lung development emphasize the integrated role of epithelial, stromal, vascular and neural cell elements in building a functional lung, while the subsequent chapters on adult lung regeneration describe the nature and properties of adult lung stem/progenitor cells distributed along the proximal-distal axis of the airway tree. The chapters on regulation of lung regeneration and repair discuss how regenerative cells interact with their niche microenvironment and how regulation of lung regeneration and repair in the steady state and following injury recapitulates ontogeny. And, lastly, the chapters on cellular therapies for lung disease and bioengineering the lung focus on promising emerging therapies and approaches in lung regenerative medicine. The scope of this volume of the Stem Cell Biology and Regenerative Medicine series focuses on exploring the topic of building and rebuilding the lung from a cellular rather than a molecular perspective. Thus, the section on cellular therapies does not include extensive coverage of each of the numerous lung diseases, including cancer, which could be amenable to stem cell-based therapies, although the final chapter does include some discussion on the future prospects and challenges. All of the contributors are working on the cutting edge of the lung stem cell field, making this book essential reading for those with an interest in the field of lung stem cell biology and the potential role of cellular therapies and tissue bioengineering approaches in lung regenerative medicine, including biomedical scientists, graduate students, post-graduate researchers and respiratory clinicians.

The use of stem cells to help with lung regeneration and repair is a novel therapy which could help phase out the need for conventional surgical or pharmacological approaches currently employed to treat diseases of the lung or other organs. The present book explores all avenues of this new form of medical care, moving swiftly, but in depth, from the basic science of lung development, to the analyses of different stem cell types available for regeneration and on to the application of this knowledge base in initial clinical trials.In this volume a stellar group of researchers converge, from different angles, to help towards clarifying the basic mechanisms of lung repair. These range from basic concepts of regeneration and lung development, the analyses of a variety of cell types that may be involved in lung repair, to ways of creating complex lung structures, including artificial and bioartificial lungs. The book offers an insight into repair mechanisms of the diseased lung, the role of specific lung niches and provides information on initial clinical trials as well as the use of stem cells as vehicles for gene therapy. Ingenious technological aspects of assessing stem cell engraftment of stem cell bioprocessing are also included in this volume./a

Over the past decade, significant efforts have been made to develop stem cell-based therapies for difficult to treat diseases. Multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), appear to hold great promise in regards to a regenerative cell-based therapy for the treatment of these diseases. Currently, more than 200 clinical trials are underway worldwide exploring the use of MSCs for the treatment of a wide range of disorders including bone, cartilage and tendon damage, myocardial infarction, graft-versus-host disease, Crohn’s disease, diabetes, multiple sclerosis, critical limb ischemia and many others. MSCs were first identified by Friendenstein and colleagues as an adherent stromal cell population within the bone marrow with the ability to form clonogenic colonies in vitro. In regards to the basic biology associated with MSCs, there has been tremendous progress towards understanding this cell population’s phenotype and function from a range of tissue sources. Despite enormous progress and an overall increased understanding of MSCs at the molecular and cellular level, several critical questions remain to be answered in regards to the use of these cells in therapeutic applications. Clinically, both autologous and allogenic approaches for the transplantation of MSCs are being explored. Several of the processing steps needed for the clinical application of MSCs, including isolation from various tissues, scalable in vitro expansion, cell banking, dose preparation, quality control parameters, delivery methods and numerous others are being extensively studied. Despite a significant number of ongoing clinical trials, none of the current therapeutic approaches have, at this point, become a standard of care treatment. Although exceptionally promising, the clinical translation of MSC-based therapies is still a work in progress. The extensive number of ongoing clinical trials is expected to provide a clearer path forward for the realization and implementation of MSCs in regenerative medicine. Towards this end, reviews of current clinical trial results and discussions of relevant topics association with the clinical application of MSCs are compiled in this book from some of the leading researchers in this exciting and rapidly advancing field. Although not absolutely all-inclusive, we hope the chapters within this book can promote and enable a better understanding of the translation of MSCs from bench-to-bedside and inspire researchers to further explore this promising and quickly evolving field.

Most organs in the adult human body are able to maintain themselves and undergo repair after injury; these processes are largely dependent on stem cells. In this Monograph, the Guest Editors bring together leading authors in the field to provide information about the different classes of stem cells present both in the developing and adult lung: where they are found, how they function in homeostasis and pathologic conditions, the mechanisms that regulate their behaviour, and how they may be harnessed for therapeutic purposes. The book focuses on stem cells in the mouse and human lung but also includes the ferret as an increasingly important new model organism. Chapters also discuss how lung tissue, including endogenous stem cells, can be generated in vitro from pluripotent stem cell lines. This state-of-the-art collection comprehensively covers one of the most exciting areas of respiratory science

In this state-of-the-art exploration of a hugely dynamic and fast-evolving field of research, leading researchers share their collective wisdom on the role that stem cells could play in the context of physiological stress and lung injury. The text focuses on reviewing the most relevant—and recent—ideas on using local, endogenous, and exogenous progenitor/stem cells in preventing and treating injury to the lung. The lungs are one of the most complex organs in the human body, with a mature adult lung boasting at least 40 morphologically differentiated cell lineages. Our entire blood supply passes through the lung’s alveolar units during oxygenation. This interaction with the outside world, along with the intricacies of its structure, makes the lung a highly susceptible organ that is vulnerable to numerous types of injury and infection. This means that the mechanisms of lung repair are in themselves correspondingly complex. Because of their multipotentiality, as well as the fact of the lung’s relatively rapid cell turnover, stem cells are thought to be an important alternative cell-base therapy in lung injury. Despite the controversial nature of stem cell research, there has been growing interest in both local and endogenous stem cells in the lung. This highly topical book with chapters on everything from using mesenchymal stem cells in lung repair to the effect of physical activity on the mobilization of stem and progenitor cells, represents an exciting body of work by outstanding investigators and will be required reading for those with an interest in the subject.

This book covers the identification and role of endogenous lung stem cells in health and disease, particularly the most recent advances. In addition, it discusses the rapidly growing field of stem cells and cell therapy as it relates to lung biology and disease as well as ex vivo lung bioengineering. Such approaches may provide novel therapeutic approaches for lung diseases. Human pluripotent stem cell differentiation to model the pulmonary epithelium and vasculature is also discussed. World-recognized scientists who specialize in studying both the lung epithelium and pulmonary vasculature contribute the chapters. Topics covered include: stem cell niches in the lung, the role of progenitor cells in fibrosis and asthma, iPSC in modeling lung disease, vascular repair by endothelial progenitor cells and circulating fibrocytes in pulmonary vascular remodeling. This volume of the Stem Cell Biology and Regenerative Medicine series is essential reading for researchers and clinicians interested in stem cells, lung biology and regenerative medicine. It is also an invaluable resource for advanced students studying cell biology, regenerative medicine and lung physiology.

Since different types of stem cells for therapeutic applications have recently been proposed, this timely volume explores various sources of stem cells for tissue and organ regeneration and discusses their advantages and limitations. Also discussed are pros and cons for using embryonic stem cells, induced pluripotent stem cells, and adult stem cells isolated from postnatal tissues. Different types of adult stem cells for therapeutic applications are also reviewed, including hematopoietic stem cells, epidermal stem cells, endothelial progenitors, neural stem cells, mesenchymal stem cells, and very small embryonic-like stem cells. This book also addresses paracrine effects of stem cells in regenerative medicine that are mediated by extracellular microvesicles and soluble secretome. Finally, potential applications of stem cells in cardiology, gastroenterology, neurology, immunotherapy, and aging are presented. This is an ideal book for students and researchers working in the stem cell research field.