Stem Cell Therapy for Autoimmune Disease
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Edited By:Richard K. Burt M.D.Northwestern University Medical School Chief
Alberto Marmont, M.D. Published: 2004-05-10 This book may be purchased as an eBook (pdf) for $99, or individual chapters (pdf) may be purchased from the list below for $19. |
Chapters available from this book
Allogeneic Hematopoietic Stem Cell Transplantation for Autoimmune Diseases
Shimon Slavin, Alberto Marmont and Richard K. Burt
Autoimmune diseases result from self-reactive T-lymphocytes and autoantibodies, produced most likely in cooperation with T-cell dependent B-cells. Until recently, non-specific suppression of self-reactive lymphocytes or the inflammatory process mediated by the ongoing anti-self reactivity repres...
Autologous Stem Cell Transplantation in Relapsing Polychondritis
Falk Hiepe, Andreas Thiel, Oliver Rosen, Gero Massenkeil, Gerd-Rodiger Burmester, Andreas Radbruch and Renate Arnold
Relapsing polychondritis is a rare multisystem autoimmune disorder of unknown etiology that was first described by Jaksch-Wartenhorst in 1923.1 It is an episodic and progressive inflammatory disease of the cartilaginous structures, including the elastic cartilage of the ear and nose, the hyaline...
Bronchial Asthma and Idiopathic Pulmonary Fibrosis as Potential Targets for Hematopoietic Stem Cell Transplantation
Jślio C. Voltarelli, Eduardo A. Donadi, José A. B. Martinez, Elcio O. Vianna and Willy Sarti
In this chapter we examined existing evidence supporting the application of hematopoietic stem cell transplantation (HSCT) for the treatment of severe and refractory cases of bronchial asthma or idiopathic pulmonary fibrosis (IPF). Both diseases share chronic inflammatory features mediated by bo...
Autologous Hematopoietic Stem Cell Transplantation for Crohn’s Disease
Robert M. Craig and Richard K. Burt
Autologous hematopoietic stem cell transplantation (HSCT) is being explored as therapy for autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. Recently, our medical center performed the first four HSCTs in the world for patients with severe ...
Hematopoietic Stem Cell Transplantation as Treatment for Type 1 Diabetes
Jślio C. Voltarelli, Richard K. Burt, Norma Kenyon, Dixon B. Kaufman and Elizabeth C. Squiers
Type 1 diabetes mellitus is an autoimmune disease associated with B cell derived antibodies and T cell proliferative responses to a variety of islet cell peptides. Near normalization of blood sugar levels as monitored by glycosylated hemoglobin (HgbA1C) diminishes diabetic secondary complication...
Autologous Hematopoietic Stem CellTransplantation for Idiopathic Inflammatory Myositis
Yu Oyama, Walter G. Barr and Richard K. Burt
The term idiopathic inflammatory myopathies (IIM) refers to a group of disorders of unknown cause in which immune-mediated inflammation results in muscle injury and complaints of weakness. IIM consist of six distinct subtypes including: type I- primary idiopathic polymyositis (PM), type II- pri...
Hematopoietic Stem Cell Transplantation in Patients with Autoimmune Bullous Skin Disorders
Joan Guitart and Richard K. Burt
There is an array of primary skin disorders that have been considered autoimmune diseases in their pathogenesis. Most of them are proven to have pathogenic autoantibodies that react against specific antigens on the cell surface of the keratinocytes or basement membrane components. Patients with ...
Hematopoietic Stem Cell Therapy for Patients with Refractory Myasthenia Gravis
Richard K. Burt
Myasthenia gravis (MG), which means severe muscle weakness, is due to antibody mediated loss of motor end plate acetylcholine (ACh) receptors.1,2 In normal muscle, acetylcholine released from a nerve ending binds to the acetylcholine receptor (AChR) on the post synaptic motor end plate of muscl...
Hematopoietic Stem Cell Transplantation in the Treatment of Chronic Inflammatory Demyelinating Polyradiculoneuropathy
George Hutton, Yu Oyama, Richard K. Burt and Uday Popat
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune mediated neuropathy. The characteristic clinical picture is one of slowly progressive weakness and sensory loss. Muscle stretch reflexes are depressed or absent. The diagnosis is supported by findings of elev...
High-Dose Chemotherapy with Haematopoietic Stem Cell Transplantation in Primary Systemic Vasculitis, Behcet's Disease and Sjogren’s Syndrome
Christoph Fiehn and Manfred Hensel
The potential role of intensive immunosuppression and hematopoietic stem cell transplantation in the treatment of severe autoimmune diseases has been evaluated for several years. A cure seems to be possible in some cases. “Resetting” of the immune system (rather than deletion of the auto-aggres...
Immunosuppressive Chemotherapy with Autologous Stem Cell Support for Chronic Autoimmune Thrombocytopenia
Richard D. Huhn, Patrick F. Fogarty, Ryotaro Nakamura and Cynthia E. Dunbar
Autoimmune idiopathic thrombocytopenia (AITP) is a disorder of low platelet counts in which antibodies directed against platelet and megakaryocyte surface proteins cause platelet destruction in reticuloendothelial organs and inhibit platelet production.1,2 A compensatory increase in marrow mega...
Hematopoietic Stem Cell Transplantation for Systemic Sclerosis
Andrew M. Yeager, Diane BuchBarker, Thomas A. Medsger, Jr. and Albert D. Donnenberg
Systemic sclerosis is a chronic disorder of connective tissue characterized by inflammation and fibrosis of, and degenerative changes in, the blood vessels, skin, synovium, skeletal muscle, and certain internal organs, especially the gastrointestinal tract, lung, heart and kidney.1 Although ther...
Immunology of Scleroderma
Carol M. Artlett
Systemic sclerosis, or scleroderma (SSc), is an autoimmune disease, which manifests clinically by progressive cutaneous and visceral fibrosis. SSc is a complex, heterogeneous disease with clinical forms ranging from limited skin involvement (lcSSc) to diffuse disease (dcSSc) causing extensive cu...
Autologous Stem Cell Transplantation for Refractory Juvenile Idiopathic Arthritis (JIA)
Nico Wulffraat
Although the overall prognosis for most children with chronic arthritis is good, a small proportion of children with systemic onset or polyarticular Juvenile Idiopathic Arthritis (JIA) are refractory to combinations of non-steroidal anti-inflammatory drugs (NSAIDS) and immunosuppressive drugs s...
Haemopoietic Stem Cell Transplantation for Rheumatoid Arthritis—World Experience and Future Trials
John A. Snowden, John J. Moore, Sarah J. Bingham, Steve Z. Pavletic and Richard K. Burt
Rheumatoid arthritis (RA) affects approximately 1% of the population. It is rarely life threatening in the short term, but, in the long term, RA and the side effects of therapy shorten life. RA causes significant disability. Of those who have the disease for more than 12 months, a majority will ...
Treatment of Rheumatoid Arthritis
Stuart Weisman and Arthur Kavanaugh
During the past decade, the approach to the treatment of patients with rheumatoid arthritis (RA) has undergone remarkable change. Non steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and conventional disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, sulfasalaz...
Hematopoietic Stem Cell Transplantation for Systemic Lupus Erythematosus
Ann E. Traynor, Richard K. Burt and Alberto Marmont
Systemic lupus erythematosus (SLE) is a systemic, clinically and genetically heterogenous disease characterized by diffuse tissue damage mediated in great part by autoimmune pathogenic reactions. Notwithstanding impressive therapeutic progress and significant amelioration of quantity and quality...
Lupus Nephritis
Annie Y. Suh and Robert M. Rosa
Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease that can affect multiple organs. Studies of new therapies for SLE often involve, or may even be confined, to individuals with renal involvement because an unambiguous endpoint may be defined, i.e., time to dialys...
Definition, Classification, Activity and Damage Indices in Systemic Lupus Erythematosus
Jennifer M. Grossman and Kenneth C. Kalunian
Systemic lupus erythematosus (SLE) is a multisystem disease that is caused by antibody production and comple ment fixing immune complex deposition that results in tissue damage. As potentially many different antibodies can be produced in SLE patients, the different organ specific targets of the...
Molecular and Cellular Pathogenesis of Systemic Lupus Erythematosus
George C. Tsokos, Yuang-Taung Juang, Christos G. Tsokos and Madhusoodana P. Nambiar
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that afflicts women during their child-bearing years. The heterogeneous clinical disease is characterized by abnormal production of autoantibodies and immune complexes in association with a diverse array of clinical manifestat...
Hematopoietic Stem Cell Transplantation for Multiple Sclerosis: Finding Equipoise
Athanasios Fassas and Richard K. Burt
In view of the lack of curative treatments, high-dose myelo/ immunosuppression with autologous stem cell transplantation (HSCT) has been utilized as therapy of multiple sclerosis (MS). HSCT has immunosuppressive and immunomodulatory effects which may tip the immunological balance towards disease...
Intense Immunosuppression Followed by Autologous Stem Cell Transplantation in Severe Multiple Sclerosis Cases: MRI and Clinical Data
G.L. Mancardi, R. Saccardi, A. Murialdo, F. Pagliai, F. Gualandi, A. Marmont, M. Inglese, P. Bruzzi, M.P. Sormani, M.G. Marrosu, G. Meucci, L. Massacesi, A. Bertolotto, A. Lugaresi, E. Merelli, M. Filippi
Multiple sclerosis (MS) is an autoimmune disease characterized by attacks against components of the myelin sheath of the central nervous system (CNS) mediated by immuno-competent cells. In the early stages, distinct relapses are followed by remission and are often trailed by a chronic phase of ...
Monitoring Disease Activity in Multiple Sclerosis
Lorri Lobeck
The search for tools to monitor disease activity in multiple sclerosis (MS) has expanded in recent years. Availability of new therapies has prompted reassessment of clinical examination scales and development of new magnetic resonance imaging (MRI) techniques to improve trial efficiency such tha...
Axonal Injury and Disease Progression in Multiple Sclerosis
Carl Bjartmar and Bruce D. Trapp
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS). Approximately one million people are affected worldwide and women outnumber men 2:1. MS is a major cause of nontraumatic neurological disability among young adults. The etiology is u...
Immunological Aspects of Multiple Sclerosis with Emphasis on the Potential Use of Autologous Hemopoietic Stem Cell Transplantation
Paolo A. Muraro, Henry F. McFarland and Roland Martin
Multiple sclerosis (MS) is one of the most intensively studied human autoimmune diseases, and belongs to the few for which immunomodulatory therapies have been approved during the last decade. Nevertheless, these treatments that include interferon-β, glatiramer acetate and mitoxantrone are...
Infection in the Hematopoeitic Stem Cell Transplant Recipient with Autoimmune Disease
Valentina Stosor and Teresa R. Zembower
Infection is a well-recognized complication of hematopoietic stem cell transplantation (HSCT). Based on decades of cumulative experience from HSCT for hematologic malignancy, there are relatively defined periods of risk for infection in the transplanted host.1-5 Vulnerability to infection is dyn...
Mobilization and Conditioning Regimens in Stem Cell Transplant for Autoimmune Diseases
Ewa Carrier and Richard K. Burt
Hematopoietic stem cell transplantation (HSCT) of autoimmune diseases has been performed as phase I/II studies in Europe, USA, Asia, and Australia. Phase III studies for systemic lupus erythematosus (SLE), multiple sclerosis (MS) and systemic sclerosis (SSc) are being designed and implemented. ...
Allogeneic Hemopoietic Stem Cell Transplantation in Animal Models of Autoimmune Disease
Susumu Ikehara
Using animal models for autoimmune diseases, we show that allogeneic bone marrow transplantation (allo BMT) can be used to treat autoimmune diseases and, in addition, provide evidence that autoimmune diseases are stem cell disorders. To apply allo BMT to humans, we have very recently establishe...
Autologous Stem Cell Transplantation in Animal Models of Autoimmune Diseases
D.W. van Bekkum
Autologous bone marrow transplantation was introduced for the treatment of severe intractable autoimmune disease (AD) following the demonstration that impressive responses could be obtained with this modality in two different animal models: adjuvant arthritis (AA) and experimental autoimmune en...
High-Dose Immune Suppression without Hematopoietic Stem Cells for Autoimmune Diseases
Robert A. Brodsky
Hematopoietic stem cell transplantation holds great promise for treating autoimmunity. The source of hematopoietic stem cells can be from a normal donor (allogeneic) or from the patient (autologous). Due to the high morbidity and mortality of traditional allogeneic stem cell transplantation, mo...
Historical Perspective and Rationale of HSCT for Autoimmune Diseases
Alberto M. Marmont
Autoimmune diseases have been defined as a fascinating but still poorly understood group of diseases,1 which pose “some of the most baffling scientific questions and daunting clinical challenges in internal medicine.”2 This intricated and still imperfectly elucidated background must be considere...
Immune Reconstitution after Hematopoietic Stem Cell Transplantation
Andreas Thiel, Tobias Alexander, Christian A. Schmidt, Falk Hiepe, Renate Arnold, Andreas Radbruch, Larissa Verda and Richard K. Burt
Qualitative and quantitative changes occur within the immune system during aging. Normal age-related T cell alterations include a decline in CD4+ cells, loss of na•ve (antigenic virgin) cells, increase in memory (antigen experienced) cells, decline in T cell proliferative responses, and narrowin...
Molecular Analysis of Immunity
Daniel Douek
The molecular analysis of immunity means just that: the analysis, at the molecular level, of the ability to mount an immune response. It is an analysis of function rather than status. As such, it is critical to understand that although we are able to identify many aspects of the immune system in...
Evidence for a Role of Infections in the Activation of Autoreactive T Cells and the Pathogenesis of Autoimmunity
J. Ludovic Croxford and Stephen D. Miller
The immune system provides protection against infection by microorganisms. The first line of defense against infectious pathogens is the innate immune response by neutrophils, NK cells, and macrophages, which differentiates between foreign organisms (nonself ) and self-tissue, by recognizing “p...
Drug-Induced Autoimmunity
Robert L. Rubin and Anke Kretz-Rommel
Exposure to a wide variety of synthetic compounds has been causally related to the induction of autoimmunity. The vast majority of implicated agents are deliberately ingested medications, and these are associated most often with development of lupus-like signs and/or symptoms. However, it is use...
Analyzing Complex Polygenic Traits: The Role of Non-HLA Genes in the Susceptibility to Autoimmune Disorders
Bernard R. Lauwerys and Edward K. Wakeland
Genetic predisposition plays an important role in the susceptibility to autoimmune disorders. Evidence supporting the contribution of genetic factors include disease concordance in monozygotic twins, occasional familial clustering of related or even unrelated autoimmune conditions and increased ...
Major Histocompatibility Complex and Autoimmune Disease
Ursula Holzer and Gerald T. Nepom
The major histocompatibility complex (MHC) encodes a large number of molecules which are key participants in the function of the immune system. Included in the human MHC, known as human leukocyte antigen (HLA), are two classes of HLA molecules which are highly polymorphic, and which provide gen...
CD4+ T Regulatory Cells and Modulation of Undesired Immune Responses
Rosa Bacchetta, Megan K. Levings and Maria-Grazia Roncarolo
T regulatory (Tr) cells are a distinct population of T cells which modulate T helper Th1 and Th2 mediated immuno-responses and maintain immunological homeostasis. Thus far, Tr type 1 (Tr1) cells and CD4+CD25+ T cells are the best characterized subsets of CD4+ Tr cells. Both types of Tr cells sh...
Dendritic Cells Control the Balance between Tolerance and Autoimmunity
Simon W. F. Milling and G. Gordon MacPherson
Since their first description in 1973,1 many important roles have been described for dendritic cells (DC) in the induction of immunity. DCs are a heterogeneous population of bone marrow derived leukocytes that efficiently link the innate and adaptive immune systems and play a crucial part in ini...
Shifting Paradigms in Peripheral Tolerance
Jonathan D. Powell and Ronald H. Schwartz
Through clonal selection, the immune system is able to prepare and respond to a multitude of diverse antigens. However, since the generation of diversity is a stochastic post-germline encoded event, a critical component of the immune response must subsequently be the ability to discern between ...
Death Receptor-Mediated Apoptosis and Lymphocyte Homeostasis
Lixin Zheng, Richard M. Siegel, Jagan R. Muppidi, Felicita Hornung and Michael J. Lenardo
To generate specific immunity, T and B lymphocyte clones may expand massively in response to antigenic stimulation. The expansion of antigen-specific lymphocytes allows the immune system to control pathogens and possibly neoplasia. However, in order to maintain homeostasis, a clonotypic contrac...
Overview of Immune Tolerance Strategies
Charles J. Hackett and Helen Quill
Increased understanding of immune cell activation and regulation makes plausible the development of clinical strategies to control unwanted immune responses in a specific manner. The normal safeguards collectively termed immune tolerance refer to the immune system’s ability to control and preven...
The Etiopathogenesis of Autoimmunity
Howard Amital and Yehuda Shoenfeld
Diverse and complex mechanisms take part in the induction of an autoimmune condition. An appropriate genetic and hormonal setting, a concurrent infection or vaccination and many other environmental factors all converge in the pathogenesis of autoimmunity. Various processes take part in the indu...
Adult Stem Cell Plasticity
Sean Lee and Diane S. Krause
The concept that bone marrow derived stem cells (BMSC) can give rise to cells of disparate lineages began to gain widespread support in 1998, as articles first surfaced describing the presence of marrow-derived myocytes and hepatocytes in bone marrow transplant recipient mice. Subsequent report...
The Stem Cell Continuum: A Plastic Plasticity
Peter J. Quesenberry, Jean-Francois Lambert, Gerald A. Colvin, Mark Dooner, Christine I. McAuliffe, Mehrdad Abedi, Deborah Greer, Delia Demers, Jan Cerny, Brian E. Moore, Evangelos Badiavas and Vincent Falanga
Conventional models of hematopoietic regulation propose that a primitive undifferentiated stem cell produces progeny with progressively more lineage restriction and lineage specific function and less renewal, proliferative and differentiation potential. The stem cell itself has tremendous proli...
Clinical Trials of Hematopoietic Stem Cells for Cardiac and Peripheral Vascular Diseases
Hiroaki Matsubara
Blood vessels are primarily composed of two cell types: endothelial cells, lining the inside and smooth muscle cells, covering the outside. While angiogenesis research has generally been focused on these two vascular cell types, recent evidence indicates that the bone marrow may also contribute ...
Regeneration of Cardiomyocytes from Bone Marrow Stem Cells and Application to Cell Transplantation Therapy
Keiichi Fukuda
Although heart transplantation is the ultimate therapy for the treatment of severe heart failure, it has not been widely examined, because it requires donor hearts, and the inadequate supply of donor hearts is often a major problem everywhere in the world. As a result, the current challenge in ...
Properties and Therapeutic Potentials of Adult Stem Cells from Bone Marrow Stroma (MSCs)
Darwin J. Prockop
In addition to hematopoietic stem cells, bone marrow contains a second class of adult stem cells that have been referred to as fibroblastoid colony-forming units, nonhematopoietic mesenchymal stem cells or marrow stromal cells (MSCs). MSCs have attracted increasing attention for their potential...
Hematopoietic Stem Cell Biology: Relevance to Autoimmunity
Richard J. Jones
Animal models have been helpful in better understanding the biology of both hematopoietic stem cells (HSC) and autoimmunity. Autoimmunity is caused by a complex interplay of genetic and environmental factors. Spontaneous animal models of autoimmunity result from germ-line mutations; these inclu...
Adipose Tissue-Derived Adult Stem Cells: Potential for Cell Therapy
Laura Aust, Lyndon Cooper, Blythe Devlin, Tracey du Laney, Sandra Foster, Jeffrey M. Gimble, Farshid Guilak, Yuan Di C. Halvorsen, Kevin Hicok, Amy Kloster, Henry E. Rice, Anindita Sen, Robert W. Storms and William O. Wilkison
The term “adult stem cell” has traditionally been used to refer to the hematopoietic progenitors isolated from bone marrow and transplanted into patients after high dose chemotherapy. Until recently, cell differentiation was conceptualized in a step-wise, unidirectional process. Unique progenito...
Turning Blood into Liver
Bryon E. Petersen and Neil D. Theise
Hepatic oval “stem” cells have been studied in rodents since the mid-1950s when they were first described by E. Farber.1 Hepatic oval “stem” cells have been shown to be a cell type capable of developing into hepatocytes or bile duct epithelial cells.2,3 Numerous in vivo and in vitro studies hav...
Neural Stem Cells and Oligodendrocyte Progenitors in the Central Nervous System
Jennifer A. Jackson and Diana L. Clarke
The adult vertebrate central nervous system (CNS) consists of four major differentiated cell types: neurons, astrocytes, oligodendrocytes and ependymal cells. Historically, there has been disagreement on how these differentiated cell types are generated in the CNS. Progress remains hindered by t...
Embryonic Stem Cells: Unique Potential to Treat Autoimmune Diseases
Dan S. Kaufman and James A. Thomson
Embryonic stem (ES) cells are pluripotent cells that can be maintained indefinitely in culture as undifferentiated cell lines, yet retain their ability to form any cell type. The derivation of human embryonic stem cells provides a new model system to learn about human developmental biology. Thes...
PREFACE and Frontmatter The Immune System and Its Treatment with Stem Cell Therapy: Creator, Preserver, and Destroyer
Richard Burt
The creation of something new means loss of the old, while destruction means, for better or worse, a new beginning. This duality of existence is an element of Eastern religions and philosophies. For example, Shiva, the Hindu Deity of creation and preservation, is also the God of destruction. The...
When is a Stem Cell Really a Stem Cell?
Gerald J. Spangrude
In recent years, data from numerous experimental studies has suggested that the potential uses of stem cells in medicine may reach far beyond bone marrow transplantation. How applicable is recent research to modern medicine, and how soon might we expect to see stem cells applied to tissue engine...
