Stem Cell Transplantation For Autoimmune Diseases And Inflammation

This book introduces many new technologies and clinical applications of hematopoietic stem cells and mesenchymal stem cell transplantation for the treatment of autoimmune diseases and inflammatory diseases. Presented in two parts, Part 1 focuses on stem cell therapies for autoimmune disease treatment; Part 2 focuses on stem cell therapies and their application in the treatment of common inflammatory diseases, including chronic knee osteoarthritis, chronic obstructive pulmonary disease, liver cirrhosis, Crohn's Disease, Multiple Sclerosis, and more. This book is an essential source for all advanced students and researchers involved with these diseases, stem cells, or both. Stem Cell Transplantation for Autoimmune Diseases and Inflammation and the other books in the Stem Cells in Clinical Applications series are invaluable to scientists, researchers, advanced students and clinicians working in stem cells, regenerative medicine, or tissue engineering as well as cancer or genetics research.

Stem cell transplantation may be complicated by treatment-related mortality and like the immune system that it regenerates has equal potential to either create and preserve or destroy. The dual nature that defines stem cells is differentiation that ultimately leads to death and self-renewal, which leads to immortality. What types of stem cells are there? How are they collected? What are their attributes and characteristics? This textbook devotes many chapters to familiarize the reader with the basic science, clinical aspects, and new questions being raised in the field of stem cell biology. Blood stem cells for tolerance and tissue regeneration are a rapidly developing research and clinical field that is being applied to autoimmune diseases. In clinical trials, autologous hematopoietic (blood) stem cells are being used to reduce the cytopenic interval following intense immune suppressive transplant regimens. While as yet not delineated, some possible mechanisms and pathways leading to tolerance after hematopoietic stem cell transplantation are suggested in these chapters. Tissue regeneration from blood stem cells is also suggested by animal experiments on stem cell plasticity or metamoirosis (i.e., change in fate) as described within this textbook. Ongoing early clinical trials on tissue regeneration from blood stem cells are described in the chapter on stem cell therapy for cardiac and peripheral vascular disease. Whether autologous hematopoietic stem cells, through the process of mobilization and reinfusion, may be manipulated to contribute to tissue repair in autoimmune diseases is a future area for translational research.

Key Features Outlines therapies and techniques for HSCT for autoimmune diseases, and d Discusses its the advantages of HSCT over conventional therapies Reviews the entire process of stem cell therapy from harvest and ethics to indications of efficacy.

Autologous hematopoietic stem cell transplantation (AHSCT) was proposed 20 years ago as an alternative therapeutic approach for patients with severe and refractory autoimmune diseases. Since then, this innovative therapy has been successfully used to treat several autoimmune diseases, such as neurological disorders (Multiple Sclerosis), connective tissue diseases (Systemic Sclerosis and Systemic Lupus Erythematous), gastrointestinal inflammatory diseases (Crohn’s Disease) and others (Juvenile Arthritis, Type 1 Diabetes, Vasculitis). Experience in phase I-II and III clinical trials over the years has led to increased safety and efficacy of this procedure. Recent studies have demonstrated superior therapeutic efficacy of AHSCT versus conventional therapies, showing that transplantation can induce long-term disease remission in the absence of any further immunosuppressive treatment. Immune monitoring studies have showed that AHSCT is able to reduce the inflammatory milieu, to reset the immune balance and to promote the generation of a new auto-tolerant immune repertoire. However, some patients fail to remain in remission, and disease is re-activated after some time post-transplantation. This scenario indicates that further immunological interventions may be still required to improve AHSCT efficacy. Clear understanding of the operating immune mechanisms that contribute to specific clinical outcomes is vital to enable improvement of AHSCT protocols for autoimmune diseases.

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.

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 is another attempt of InTechOpen to continue the dissemination of international knowledge and experience in the field of immunology. The present book includes a number of modern concepts of specialists and experts in the field of immunotherapy, covering the major topics and analyzing the history, current stage, and future ideas of application of modern immunomodulation. It is always a benefit, but also a compliment, to gather a team of internationally distinguished authors and to motivate them to reveal their expertise for the benefit of medical science and health practice. On behalf of all readers, immunologists, immunogeneticists, biologists, oncologists, microbiologists, virologists, hematologists, chemotherapists, health-care experts, as well as students and medical specialists, also on my personal behalf, I would like to extend my gratitude and highest appreciation to InTechOpen for giving me the unique chance to be the editor of this exclusive book.

Non-myeloablative allogeneic stem cell transplantation (also known as mini-transplantation or reduced-intensity conditioning transplantation) is a major advance in the field of hematopoietic transplantation within the last 5 years. This approach uses non-cytotoxic or reduced-intensity cytotoxic therapy to prepare patients for allografting of hematopoietic stem cells and lymphocytes. It has the potential to deliver the potent anti-tumor immunotherapy and bone marrow replacement capacity of allogeneic stem cell transplantation to patients with reduced treatment-related morbidity and mortality. It may also enable allogeneic transplantation in patients who would be considered ineligible for conventional transplants because of co-morbidity or advanced age. However, this approach may necessitate more careful monitoring of post-transplant chimerism and malignant disease-status than is usual with conventional allografting. There is also controversy regarding the best preparative regimen and graft-versus-host disease prophylaxis to use.