Mesenchymal Stem Cells And Immunomodulation

This essential volume explores mesenchymal stem cells (MSCs) and their potential to suppress immune-mediated inflammation. The chapters examine applications in autoimmune diseases such as lupus, rheumatoid arthritis and multiple sclerosis; blood cancers such as leukemia and lymphoma; and reproductive complications, specifically pre-term labor and use of MSCs in vitro and in animal models to discover methods of suppressing the causal inflammatory response. It also further defines the methodologies required to develop research on MSCs in vitro into established preclinical animal models including those which are proven replicas of autoimmunity and pre-term labor, to name but two. Mesenchymal Stem Cells and Immunomodulation, part of Springer’s Stem Cell Biology and Regenerative Medicine, is an invaluable resource for researchers and clinicians working with stem cells, autoimmune disease, oncology, and reproductive medicine.

Immune Response Activation and Immunomodulation has been written to address the perceived needs of both medical school and undergraduate curricula and to take advantage of new understandings in immunology. We have tried to achieve several goals and present the most important principles governing the function of the immune system. Our fundamental objective has been to synthesize the key concepts from the vast amount of experimental data that have emerged in the rapidly advancing field of immunology. The choice of what is most important is based on what is most clearly established by experimentation, what our students find puzzling, and what explains the wonderful efficiency and economy of the immune system. Inevitably, however, such a choice will have an element of bias, and our bias is toward emphasizing the cellular interactions in immune response by limiting the description of many of the underlying biochemical and molecular mechanisms to the essential facts. This book gives an insight into the role of cytokines in activating immune response during pathogenic invasion. Immunomodulation, aryl hydrocarbons, the role of the protein defensin and nucleated cells in provoking immune response, Bcl protein/gene-based apoptotic pathways, and plant-derived phytochemical-mediated immune response are all central themes of this book.

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.

Multipotent mesenchymal stem cells (MSCs) are a heterogeneous population of cells which reside in a variety of tissues. They differentiate into several mesodermal lineages, secrete a multitude of trophic factors and contribute to tissue homeostasis. MSCs are able to exert immunosuppressive activities by interfering with inflammatory cytokine production and with T- and B-cell proliferation. These immunomodulating properties make MSCs promising candidates for the treatment of chronic inflammatory and autoimmune disorders. There are, however, certain caveats involved including inappropriate migration of cells in the body, immune rejection, tumor formation, or graft versus host disease (GvHD). This book investigates the current state of the MSC-dependent therapy of chronic inflammatory disorders and autoimmune diseases. Among the covered topics are GvHD, chronic kidney, liver and lung disease, ischemic heart and inflammatory bowel disease, diabetes, osteoarthritis, various rheumatic and neurological disorders and, lastly, tumors and solid organ transplantations. This book also questions the immunoprivileged status of MSCs, discusses the therapeutic role of MSCs in experimental animal disease models and their translation to the corresponding human disorders, envisions a role for MSCs in tumor interventions and, lastly, describes a systems biology approach for stem cells and inflammation.

This book focuses on mesenchymal stem cells (MSCs) of animal origin, including their isolation, characterization, and clinical applications. After briefly discussing the historical development of the field of stem cell research, it describes the basic properties and nature of stem cells particularly in relation to MSCs. In turn, it reviews materials and methods used to isolate MSCs from various sources, culture expansion, characterization and long-term storage. It also explores the therapeutic efficacy, immunomodulation and anti-inflammatory, and differentiation properties of MSCs. Importantly, the book discusses the applications of genetic engineering to enhance the efficacy and potential of MSCs in regenerative medicine. The book largely addresses the potential applications of mesenchymal stem cells in therapies for important species of domesticated animals including sheep, goats, cattle, buffalo, cats, dogs and horses. Finally, the book presents an abridgement of challenges and future prospects of stem cell research and application in medicine, in general and veterinary sciences, in particular.

This book is a comprehensive overview of the recent developments in the clinical and research fields of mesenchymal stem cells (MSCs). It is divided into three main sections that cover a wide range of topics including sources and functions of MSCs, their therapeutic applications, their role in tissue engineering, and the application of pharmacologic intelligence in research and development of MSCs.

Mesenchymal Stem Cells in Human Health and Diseases provides a contemporary overview of the fast-moving field of MSC biology, regenerative medicine and therapeutics. MSCs offer the potential to dramatically reduce human suffering from disease. Numerous MSC-based studies are ongoing each year, each offering hope for novel treatments in human disease. This book provides information on MSC application in well-studied human diseases and tissue repair/regeneration and recent advances in their research and treatment. These discoveries are placed within the structural context of tissue and developmental biology in sections dealing with recent advances in our understanding of MSC biology. Includes insights ranging from MSC biology and development through the derivation and identification and properties of MSCs Helps to identify potential innovative solutions for restoring normal morphogenesis and/or regeneration of diseased organs Discusses the fact-based promise of MSC therapeutics and regenerative medicine in the real world