Stem Cell-Dependent Therapies: Mesenchymal Stem Cells in Chronic Inflammatory Disorders

• Publisher: De Gruyter
• Year: 2013
• Tongue: English
• Leaves: 428
• Category: Library

✦ Synopsis

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.

• An important contribution to the exciting field of regenerative medicine
• Unique focus on aspects of inflammation / anti-inflammation and their implication for regeneration
• Treats bone-, tendon, cartilage and heart regeneration
• Full color illustrations

✦ Table of Contents

Preface
Contributing authors
1 Mesenchymal stem cells in the context of stem cell biology
1.1 Introduction – Definitions
1.2 Embryonic and adult tissue stem cells
1.3 Adult tissue stem cells and progenitors
1.4 Adult stem cells and tissue homeostasis
1.5 Adult stem cell niches
1.6 Commitment and differentiation
1.7 The case for bone marrow MSCs
1.8 Clinical prospects
1.9 Concluding remark
References
2 Are mesenchymal stem cells immune privileged?
2.1 Introduction – Definition of mesenchymal stem cells (MSCs)
2.2 The immunosuppressive effect of MSCs on immune cells
2.3 The potential clinical benefits of MSCs as immunosuppressants
2.4 The mechanisms of immunosuppression by MSCs
2.5 The mechanisms of immunosuppression by human MSCs
2.6 Immunosuppression by murine MSCs and the species difference underlying the mechanisms of immunosuppression by MSCs
2.7 Immunosuppression mediated by fibroblasts
2.8 The mechanisms of the immunosuppressive effect of MSCs are shared with other nonstromal cells
2.9 How long can MSCs survive in vivo?
2.10 Conclusion and discussion
References
3 Mesenchymal stem cell therapies for autoimmune diseases
3.1 Introduction
3.2 Autoimmune disease
3.3 Mesenchymal stem cells (MSCs)
3.3.1 Animal models
3.4 Results of MSCs clinical trials
3.5 Safety of MSCs
3.6 Conclusion
References
4 Mesenchymal stem cells in osteoarthritis and rheumatic disease
4.1 Introduction – Rheumatic diseases
4.2 Rheumatoid arthritis (RA)
4.3 Osteoarthritis (OA)
4.4 MSCs in healthy and rheumatic joint tissues
4.5 Application of MSCs in rheumatic diseases
4.6 MSCs application in animals
4.7 Clinical studies in humans
4.8 Risks and benefits of MSCs treatments in rheumatic diseases
References
5 Mesenchymal stem cells in enthesis formation and repair
5.1 Introduction
5.2 Structure of the tendon-to-bone junction
5.3 Enthesis resident T cells are involved in enthesopathies provoking inflammation and bone remodeling
5.4 Biomaterials and growth factor-dependent regeneration of tendon-to-bone junctions
5.5 Biomechanical stimulation for enthesis repair
5.6 Mesenchymal stem cells (MSCs)
5.7 Stem cell-dependent approaches for repair of osteotendinous junctions
5.8 Stem cell-dependent delivery of growth factors
5.9 Stem cell-dependent delivery of tenogenic transcription factors
5.10 Stem cell-dependent delivery of matrix metalloproteinases
5.11 Trophic activities of MSCs in enthesis repair
5.12 Outlook
Acknowledgment
References
6 Mesenchymal stem cells for clinical/therapeutic interventions of graft-versus-host disease
6.1 Clinical graft-versus-host disease
6.2 Chronic graft-versus-host disease
6.3 Rationale to use mesenchymal stromal cells for treatment of GvHD
6.4 Experience of MSCs in clinical acute graft-versus-host disease
6.5 Treatment of acute GvHD with stromal cells from alternate sources, adipose tissue-derived, umbilical cord blood-derived or fetal membrane-derived stromal cells
6.6 Mesenchymal stromal cells for treatment of chronic graft-versus-host disease
6.7 Clinical trials of prophylaxis with mesenchymal stromal cells for graft-versus-host disease
6.8 Discussion on clinical use of mesenchymal stem cells
6.9 How should we best utilize MSC treatment of GvHD?
References
7 Mesenchymal stem cells for graft-versus-host disease in experimental animal models
7.1 Introduction – Experimental models of graft-versus-host disease (GvHD)
7.2 Immunobiology of experimental GvHD
7.3 Mesenchymal stromal cells in mice
7.4 Mesenchymal stromal cells and mouse models of graft-versus-host disease
References
8 Mesenchymal stem cells and organ transplantation: initial clinical results
8.1 Introduction
8.2 Rationale for the use of MSCs in organ transplantation
8.2.1 Shortage of donor organs for transplantation
8.2.2 Ischemia-reperfusion injury
8.2.3 Chronic immunosuppression
8.3 Considerations regarding the choice of the clinical protocols
8.3.1 Definition, identity and product release criteria for human MSCs preparations
8.3.2 Source of human MSCs
8.3.3 Potential interactions between MSCs and concomitant therapy
8.3.4 Safety of MSCs-based treatments
8.4 Clinical MSCs and solid organ transplantation trials
8.4.1 Autologous MSCs in the induction phase with standard immunosuppression
8.4.2 Autologous MSCs in the induction phase with avoidance of biologics at induction and reduced maintenance immunosuppression
8.4.3 Allogeneic MSCs in the induction phase
8.4.4 Autologous MSCs for the treatment of biopsy-proven subclinical rejection, progressive renal interstitial fibrosis and tubular atrophy
8.5 Future perspectives
Acknowledgments:
References
9 Stem cell therapy in patients with ischemic heart disease
9.1 Introduction
9.2 Cell type and source for clinical therapy
9.3 Mechanisms behind regeneration of damaged myocardium
9.4 Preclinical experience with stem cells for IHD
9.5 Cell-based therapy in patients with IHD
9.6 MSCs in patients with IHD
9.7 Ongoing clinical trials using MSCs
9.8 Cell delivery and engraftment
9.9 Perspectives
9.10 Conclusion
References
10 Mesenchymal stem cells as a strategy for the treatment of multiple sclerosis and other diseases of the central nervous system
10.1 Introduction
10.2 MSCs transplantation for neurological diseases: why, which, and how
10.3 Vascular diseases: ischemic stroke
10.3.1 Preclinical studies
10.3.2 Clinical studies
10.4 Trauma spinal cord injury
10.4.1 Preclinical studies
10.4.2 Clinical studies
10.5 Extrapyramidal diseases
10.5.1 Parkinson’s disease (PD)
10.5.2 Preclinical studies
10.5.3 Clinical studies
10.5.4 Huntington’s disease (HD)
10.5.5 Preclinical studies
10.6 Multiple system atrophy (MSA)
10.6.1 Preclinical studies
10.6.2 Clinical studies
10.7 CNS demyelinating diseases: multiple sclerosis
10.7.1 Preclinical studies
10.7.2 Clinical studies
10.8 Motor neuron diseases: amyotrophic lateral sclerosis (ALS)
10.8.1 Preclinical studies
10.8.2 Clinical studies
10.9 Dementia: Alzheimer’s disease (AD)
10.9.1 Preclinical studies
10.9.2 Clinical studies
10.10 Concluding remarks
References
11 Mesenchymal stem cells for the treatment of inflammatory bowel disease
11.1 Introduction
11.2 Immunology and intestinal barrier function
11.3 Cell-based treatments for IBD
11.3.1 Hematopoietic cell transplantation
11.4 T regulatory cells (Tregs)
11.5 Mesenchymal stem cells (MSCs)
11.5.1 Immunologic basis for MSCs and IBD
11.6 MSC homing and engraftment
11.7 MSC clinical trials
11.8 Summary and future directions
References
12 Mesenchymal stem cells in chronic lung diseases: COPD and lung fibrosis
12.1 Introduction
12.2 Idiopathic pulmonary fibrosis
12.3 MSCs and animal models of fibrotic lung disorders
12.4 Chronic obstructive pulmonary disease (COPD)
12.5 Conclusions and future directions
Acknowledgments
References
13 Mesenchymal stem cells as therapeutics for liver repair and regeneration
13.1 Introduction
13.2 Cell therapy for liver disease
13.3 The ideal cell for liver regeneration
13.4 Mesenchymal stem cells (MSCs) as cellular therapeutics
13.5 MSCs for treating liver disease
13.5.1 In vitro models to study MSCs hepatic differentiation
13.5.2 In vivo models to study MSCs as cellular therapies for liver disease/injury
13.6 The fetal sheep model
13.7 Clinical trials using MSCs for liver regeneration
13.8 Summary/Conclusions:
References
14 Mesenchymal stem cells attenuate renal fibrosis
14.1 Introduction – Kidney function
14.2 Kidney dysfunction and chronic kidney disease (CDK)
14.2.1 Molecular and cellular interaction in renal fibrosis
14.3 Mesenchymal stem cells (MSCs): Definition and basic features
14.3.1 Therapeutic potential of MSCs and their mechanisms of action in the repair/regeneration of tissue injury
14.4 MSCs and kidney diseases
14.4.1 MSCs have a prominent antifibrotic effect in distinct models of experimental chronic kidney diseases
14.4.2 Mechanisms related to MSCs prevent renal fibrosis
14.5 Final considerations
References
15 Immunomodulation by mesenchymal stem cells – a potential therapeutic strategy for type 1 diabetes
15.1 Introduction
15.2 Mechanisms of immunomodulation
15.3 MSC therapy for type 1 diabetes (T1D)
15.3.1 Why does MSC therapy hold value in T1D?
15.3.2 Preclinical studies to prevent and reverse T1D
15.3.3 MSC implications in islet cell transplantation
15.3.4 MSCs and clinical trials for T1D
15.4 Safety of MSC therapy
References:
16 Fibrogenic potential of human multipotent mesenchymal stem cells in inflammatory environments
16.1 Introduction
16.2 Fibrogenic potential in ex vivo expanded MSCs
16.3 Evidence of MSCs infiltration into tumor stroma
16.4 Controversies regarding therapeutic benefits of bone marrow-derived MSCs in liver fibrosis
16.5 Limited contribution of MSCs to liver regeneration in acute liver injury
16.6 Conclusion
References
17 Mesenchymal stem cells and the tumor microenvironment
17.1 Introduction
17.2 The tumor microenvironment and its role in cancer initiation and progression
17.3 How do we define MSCs in cancer?
17.4 What are the roles of MSCs in cancer progression?
17.4.1 Effect of MSCs on tumor cell proliferation
17.4.2 MSCs promote survival
17.4.3 MSCs are proangiogenic
17.4.4 MSCs have an immunosuppressive function
17.4.5 MSCs promote epithelial to mesenchymal transition
17.5 How do tumor cells communicate with MSCs?
17.6 Are MSCs recruited by tumor cells?
17.7 Can we target MSCs in human cancer?
17.8 Conclusion
References
18 Mesenchymal stem cells as a carrier for tumor-targeting therapeutics
18.1 Introduction
18.2 Enhanced angiogenesis as a target for tumor therapy
18.3 Why current therapies are not effective enough
18.3.1 Shortcomings of current anti-angiogenic pharmaceuticals
18.4 Why mesenchymal stem cells would be useful for tumor targeting
18.4.1 The tumor-homing properties of MSCs
18.4.2 MSCs as a diagnostic tool
18.4.3 Antitumor effects of unmanipulated MSCs
18.4.4 Vesicular communication of MSCs: How MSCs can be used as a drug-delivery vehicle
18.5 MSCs as a gene product-delivering vehicle
18.5.1 Genetically modified MSCs for therapeutic delivery
18.5.2 Potential for MSCs-delivered anti-angiogenic therapies
18.5.3 MSCs-mediated tumor-homing of oncolytic adenovirus enhances tumor therapy
18.5.4 Delivery of TRAIL by genetically modified MSCs to induce apoptosis
18.5.5 Tumor-specific promoter-driving thymidine kinase (TK) expression for prodrug conversion
18.6 Methods of therapeutic MSCs administration
18.7 The advantage of MSCs being immunoprivileged
18.8 Sources of acquiring MSCs for tumor therapy
18.9 Remaining challenges for the use of MSCs to deliver therapeutics
18.9.1 The immunoprivileged nature of MSCs
18.9.2 Varying responses to MSCs depending on cancer type, injection site, etc.
18.9.3 Changes in MSCs induced by cancer cells within the tumor microenvironment
18.10 Summary and prospective
Acknowledgments
References
19 Systems biology approach to stem cells, tissues and inflammation
19.1 Introduction
19.2 Biological aspects
19.2.1 Cells are the regulatory units
19.2.2 Influence of cell number and phenotype
19.3 Technological aspects
19.3.1 Technology and type of molecules
19.3.2 When “pictures start moving”
19.4 Mathematical aspects
19.4.1 Comparative statistics and interpretation
19.4.2 Interpretation based on pre-existing knowledge
19.4.3 Network models
19.5 Systems biology of differentiation
19.6 Important tasks
19.7 Conclusion
References
Index