Gross / Häupl | Stem Cell-Dependent Therapies | E-Book | sack.de
E-Book

E-Book, Englisch, 426 Seiten

Gross / Häupl Stem Cell-Dependent Therapies

Mesenchymal Stem Cells in Chronic Inflammatory Disorders
1. Auflage 2013
ISBN: 978-3-11-029830-7
Verlag: De Gruyter
Format: PDF
 Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

Mesenchymal Stem Cells in Chronic Inflammatory Disorders

E-Book, Englisch, 426 Seiten

ISBN: 978-3-11-029830-7
Verlag: De Gruyter
Format: PDF
 Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

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.
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Zielgruppe

Molecular biologists and medical researchers in the field of rege

Autoren/Hrsg.

Gross, Gerhard
Häupl, Thomas

Fachgebiete

Weitere Infos & Material

1;Preface;5
2;Contributing authors;7
3;1 Mesenchymal stem cells in the context of stem cell biology;19
3.1;1.1 Introduction – Definitions;19
3.2;1.2 Embryonic and adult tissue stem cells;20
3.3;1.3 Adult tissue stem cells and progenitors;21
3.4;1.4 Adult stem cells and tissue homeostasis;23
3.5;1.5 Adult stem cell niches;23
3.6;1.6 Commitment and differentiation;25
3.7;1.7 The case for bone marrow MSCs;26
3.8;1.8 Clinical prospects;28
3.9;1.9 Concluding remark;29
3.10;References;29
4;2 Are mesenchymal stem cells immune privileged?;35
4.1;2.1 Introduction – Definition of mesenchymal stem cells (MSCs);35
4.2;2.2 The immunosuppressive effect of MSCs on immune cells;36
4.3;2.3 The potential clinical benefits of MSCs as immunosuppressants;38
4.4;2.4 The mechanisms of immunosuppression by MSCs;39
4.5;2.5 The mechanisms of immunosuppression by human MSCs;39
4.6;2.6 Immunosuppression by murine MSCs and the species difference underlying the mechanisms of immunosuppression by MSCs;43
4.7;2.7 Immunosuppression mediated by fibroblasts;46
4.8;2.8 The mechanisms of the immunosuppressive effect of MSCs are shared with other nonstromal cells;46
4.9;2.9 How long can MSCs survive in vivo?;46
4.10;2.10 Conclusion and discussion;47
4.11;References;49
5;3 Mesenchymal stem cell therapies for autoimmune diseases;55
5.1;3.1 Introduction;55
5.2;3.2 Autoimmune disease;57
5.3;3.3 Mesenchymal stem cells (MSCs);59
5.3.1;3.3.1 Animal models;60
5.4;3.4 Results of MSCs clinical trials;62
5.5;3.5 Safety of MSCs;63
5.6;3.6 Conclusion;63
5.7;References;64
6;4 Mesenchymal stem cells in osteoarthritis and rheumatic disease;69
6.1;4.1 Introduction – Rheumatic diseases;69
6.2;4.2 Rheumatoid arthritis (RA);69
6.3;4.3 Osteoarthritis (OA);71
6.4;4.4 MSCs in healthy and rheumatic joint tissues;73
6.5;4.5 Application of MSCs in rheumatic diseases;74
6.6;4.6 MSCs application in animals;78
6.7;4.7 Clinical studies in humans;84
6.8;4.8 Risks and benefits of MSCs treatments in rheumatic diseases;86
6.9;References;88
7;5 Mesenchymal stem cells in enthesis formation and repair;101
7.1;5.1 Introduction;101
7.2;5.2 Structure of the tendon-to-bone junction;102
7.3;5.3 Enthesis resident T cells are involved in enthesopathies provoking inflammation and bone remodeling;103
7.4;5.4 Biomaterials and growth factor-dependent regeneration of tendon-to-bone junctions;105
7.5;5.5 Biomechanical stimulation for enthesis repair;106
7.6;5.6 Mesenchymal stem cells (MSCs);106
7.7;5.7 Stem cell-dependent approaches for repair of osteotendinous junctions;107
7.8;5.8 Stem cell-dependent delivery of growth factors;109
7.9;5.9 Stem cell-dependent delivery of tenogenic transcription factors;111
7.10;5.10 Stem cell-dependent delivery of matrix metalloproteinases;112
7.11;5.11 Trophic activities of MSCs in enthesis repair;112
7.12;5.12 Outlook;113
7.13;Acknowledgment;114
7.14;References;114
8;6 Mesenchymal stem cells for clinical/therapeutic interventions of graft-versus-host disease;119
8.1;6.1 Clinical graft-versus-host disease;119
8.2;6.2 Chronic graft-versus-host disease;120
8.3;6.3 Rationale to use mesenchymal stromal cells for treatment of GvHD;121
8.4;6.4 Experience of MSCs in clinical acute graft-versus-host disease;123
8.5;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;128
8.6;6.6 Mesenchymal stromal cells for treatment of chronic graft-versus-host disease;129
8.7;6.7 Clinical trials of prophylaxis with mesenchymal stromal cells for graft-versus-host disease;131
8.8;6.8 Discussion on clinical use of mesenchymal stem cells;133
8.9;6.9 How should we best utilize MSC treatment of GvHD?;134
8.10;References;137
9;7 Mesenchymal stem cells for graft-versus-host disease in experimental animal models;143
9.1;7.1 Introduction – Experimental models of graft-versus-host disease (GvHD);143
9.2;7.2 Immunobiology of experimental GvHD;145
9.3;7.3 Mesenchymal stromal cells in mice;146
9.4;7.4 Mesenchymal stromal cells and mouse models of graft-versus-host disease;148
9.5;References;154
10;8 Mesenchymal stem cells and organ transplantation: initial clinical results;161
10.1;8.1 Introduction;161
10.2;8.2 Rationale for the use of MSCs in organ transplantation;162
10.2.1;8.2.1 Shortage of donor organs for transplantation;162
10.2.2;8.2.2 Ischemia-reperfusion injury;163
10.2.3;8.2.3 Chronic immunosuppression;163
10.3;8.3 Considerations regarding the choice of the clinical protocols;164
10.3.1;8.3.1 Definition, identity and product release criteria for human MSCs preparations;165
10.3.2;8.3.2 Source of human MSCs;165
10.3.3;8.3.3 Potential interactions between MSCs and concomitant therapy;167
10.3.4;8.3.4 Safety of MSCs-based treatments;168
10.4;8.4 Clinical MSCs and solid organ transplantation trials;169
10.4.1;8.4.1 Autologous MSCs in the induction phase with standard immunosuppression;169
10.4.2;8.4.2 Autologous MSCs in the induction phase with avoidance of biologics at induction and reduced maintenance immunosuppression;172
10.4.3;8.4.3 Allogeneic MSCs in the induction phase;173
10.4.4;8.4.4 Autologous MSCs for the treatment of biopsy-proven subclinical rejection, progressive renal interstitial fibrosis and tubular atrophy;174
10.5;8.5 Future perspectives;176
10.6;Acknowledgments:;176
10.7;References;177
11;9 Stem cell therapy in patients with ischemic heart disease;181
11.1;9.1 Introduction;181
11.2;9.2 Cell type and source for clinical therapy;183
11.3;9.3 Mechanisms behind regeneration of damaged myocardium;184
11.4;9.4 Preclinical experience with stem cells for IHD;187
11.5;9.5 Cell-based therapy in patients with IHD;187
11.6;9.6 MSCs in patients with IHD;189
11.7;9.7 Ongoing clinical trials using MSCs;192
11.8;9.8 Cell delivery and engraftment;192
11.9;9.9 Perspectives;196
11.10;9.10 Conclusion;197
11.11;References;197
12;10 Mesenchymal stem cells as a strategy for the treatment of multiple sclerosis and other diseases of the central nervous system;203
12.1;10.1 Introduction;203
12.2;10.2 MSCs transplantation for neurological diseases: why, which, and how;204
12.3;10.3 Vascular diseases: ischemic stroke;205
12.3.1;10.3.1 Preclinical studies;205
12.3.2;10.3.2 Clinical studies;207
12.4;10.4 Trauma spinal cord injury;208
12.4.1;10.4.1 Preclinical studies;209
12.4.2;10.4.2 Clinical studies;210
12.5;10.5 Extrapyramidal diseases;210
12.5.1;10.5.1 Parkinson’s disease (PD);210
12.5.2;10.5.2 Preclinical studies;211
12.5.3;10.5.3 Clinical studies;212
12.5.4;10.5.4 Huntington’s disease (HD);212
12.5.5;10.5.5 Preclinical studies;213
12.6;10.6 Multiple system atrophy (MSA);214
12.6.1;10.6.1 Preclinical studies;214
12.6.2;10.6.2 Clinical studies;215
12.7;10.7 CNS demyelinating diseases: multiple sclerosis;215
12.7.1;10.7.1 Preclinical studies;216
12.7.2;10.7.2 Clinical studies;217
12.8;10.8 Motor neuron diseases: amyotrophic lateral sclerosis (ALS);218
12.8.1;10.8.1 Preclinical studies;218
12.8.2;10.8.2 Clinical studies;219
12.9;10.9 Dementia: Alzheimer’s disease (AD);220
12.9.1;10.9.1 Preclinical studies;220
12.9.2;10.9.2 Clinical studies;221
12.10;10.10 Concluding remarks;221
12.11;References;222
13;11 Mesenchymal stem cells for the treatment of inflammatory bowel disease;229
13.1;11.1 Introduction;229
13.2;11.2 Immunology and intestinal barrier function;230
13.3;11.3 Cell-based treatments for IBD;233
13.3.1;11.3.1 Hematopoietic cell transplantation;233
13.4;11.4 T regulatory cells (Tregs);234
13.5;11.5 Mesenchymal stem cells (MSCs);235
13.5.1;11.5.1 Immunologic basis for MSCs and IBD;235
13.6;11.6 MSC homing and engraftment;237
13.7;11.7 MSC clinical trials;240
13.8;11.8 Summary and future directions;242
13.9;References;244
14;12 Mesenchymal stem cells in chronic lung diseases: COPD and lung fibrosis;251
14.1;12.1 Introduction;251
14.2;12.2 Idiopathic pulmonary fibrosis;253
14.3;12.3 MSCs and animal models of fibrotic lung disorders;256
14.4;12.4 Chronic obstructive pulmonary disease (COPD);264
14.5;12.5 Conclusions and future directions;270
14.6;Acknowledgments;271
14.7;References;271
15;13 Mesenchymal stem cells as therapeutics for liver repair and regeneration;281
15.1;13.1 Introduction;281
15.2;13.2 Cell therapy for liver disease;282
15.3;13.3 The ideal cell for liver regeneration;283
15.4;13.4 Mesenchymal stem cells (MSCs) as cellular therapeutics;284
15.5;13.5 MSCs for treating liver disease;287
15.5.1;13.5.1 In vitro models to study MSCs hepatic differentiation;287
15.5.2;13.5.2 In vivo models to study MSCs as cellular therapies for liver disease/injury;288
15.6;13.6 The fetal sheep model;291
15.7;13.7 Clinical trials using MSCs for liver regeneration;297
15.8;13.8 Summary/Conclusions:;298
15.9;References;299
16;14 Mesenchymal stem cells attenuate renal fibrosis;311
16.1;14.1 Introduction – Kidney function;311
16.2;14.2 Kidney dysfunction and chronic kidney disease (CDK);313
16.2.1;14.2.1 Molecular and cellular interaction in renal fibrosis;314
16.3;14.3 Mesenchymal stem cells (MSCs): Definition and basic features;316
16.3.1;14.3.1 Therapeutic potential of MSCs and their mechanisms of action in the repair/regeneration of tissue injury;316
16.4;14.4 MSCs and kidney diseases;319
16.4.1;14.4.1 MSCs have a prominent antifibrotic effect in distinct models of experimental chronic kidney diseases;319
16.4.2;14.4.2 Mechanisms related to MSCs prevent renal fibrosis;321
16.5;14.5 Final considerations;322
16.6;References;323
17;15 Immunomodulation by mesenchymal stem cells – a potential therapeutic strategy for type 1 diabetes;327
17.1;15.1 Introduction;327
17.2;15.2 Mechanisms of immunomodulation;328
17.3;15.3 MSC therapy for type 1 diabetes (T1D);329
17.3.1;15.3.1 Why does MSC therapy hold value in T1D?;329
17.3.2;15.3.2 Preclinical studies to prevent and reverse T1D;330
17.3.3;15.3.3 MSC implications in islet cell transplantation;331
17.3.4;15.3.4 MSCs and clinical trials for T1D;332
17.4;15.4 Safety of MSC therapy;333
17.5;References:;333
18;16 Fibrogenic potential of human multipotent mesenchymal stem cells in inflammatory environments;337
18.1;16.1 Introduction;337
18.2;16.2 Fibrogenic potential in ex vivo expanded MSCs;338
18.3;16.3 Evidence of MSCs infiltration into tumor stroma;339
18.4;16.4 Controversies regarding therapeutic benefits of bone marrow-derived MSCs in liver fibrosis;340
18.5;16.5 Limited contribution of MSCs to liver regeneration in acute liver injury;342
18.6;16.6 Conclusion;344
18.7;References;344
19;17 Mesenchymal stem cells and the tumor microenvironment;349
19.1;17.1 Introduction;349
19.2;17.2 The tumor microenvironment and its role in cancer initiation and progression;351
19.3;17.3 How do we define MSCs in cancer?;352
19.4;17.4 What are the roles of MSCs in cancer progression?;353
19.4.1;17.4.1 Effect of MSCs on tumor cell proliferation;355
19.4.2;17.4.2 MSCs promote survival;355
19.4.3;17.4.3 MSCs are proangiogenic;356
19.4.4;17.4.4 MSCs have an immunosuppressive function;356
19.4.5;17.4.5 MSCs promote epithelial to mesenchymal transition;357
19.5;17.5 How do tumor cells communicate with MSCs?;359
19.6;17.6 Are MSCs recruited by tumor cells?;361
19.7;17.7 Can we target MSCs in human cancer?;363
19.8;17.8 Conclusion;364
19.9;References;364
20;18 Mesenchymal stem cells as a carrier for tumor-targeting therapeutics;371
20.1;18.1 Introduction;371
20.2;18.2 Enhanced angiogenesis as a target for tumor therapy;372
20.3;18.3 Why current therapies are not effective enough;373
20.3.1;18.3.1 Shortcomings of current anti-angiogenic pharmaceuticals;374
20.4;18.4 Why mesenchymal stem cells would be useful for tumor targeting;376
20.4.1;18.4.1 The tumor-homing properties of MSCs;376
20.4.2;18.4.2 MSCs as a diagnostic tool;379
20.4.3;18.4.3 Antitumor effects of unmanipulated MSCs;379
20.4.4;18.4.4 Vesicular communication of MSCs: How MSCs can be used as a drug-delivery vehicle;380
20.5;18.5 MSCs as a gene product-delivering vehicle;382
20.5.1;18.5.1 Genetically modified MSCs for therapeutic delivery;382
20.5.2;18.5.2 Potential for MSCs-delivered anti-angiogenic therapies;383
20.5.3;18.5.3 MSCs-mediated tumor-homing of oncolytic adenovirus enhances tumor therapy;384
20.5.4;18.5.4 Delivery of TRAIL by genetically modified MSCs to induce apoptosis;385
20.5.5;18.5.5 Tumor-specific promoter-driving thymidine kinase (TK) expression for prodrug conversion;385
20.6;18.6 Methods of therapeutic MSCs administration;387
20.7;18.7 The advantage of MSCs being immunoprivileged;388
20.8;18.8 Sources of acquiring MSCs for tumor therapy;389
20.9;18.9 Remaining challenges for the use of MSCs to deliver therapeutics;390
20.9.1;18.9.1 The immunoprivileged nature of MSCs;390
20.9.2;18.9.2 Varying responses to MSCs depending on cancer type, injection site, etc.;390
20.9.3;18.9.3 Changes in MSCs induced by cancer cells within the tumor microenvironment;391
20.10;18.10 Summary and prospective;393
20.11;Acknowledgments;393
20.12;References;394
21;19 Systems biology approach to stem cells, tissues and inflammation;399
21.1;19.1 Introduction;399
21.2;19.2 Biological aspects;400
21.2.1;19.2.1 Cells are the regulatory units;400
21.2.2;19.2.2 Influence of cell number and phenotype;401
21.3;19.3 Technological aspects;401
21.3.1;19.3.1 Technology and type of molecules;401
21.3.2;19.3.2 When “pictures start moving”;402
21.4;19.4 Mathematical aspects;403
21.4.1;19.4.1 Comparative statistics and interpretation;403
21.4.2;19.4.2 Interpretation based on pre-existing knowledge;404
21.4.3;19.4.3 Network models;404
21.5;19.5 Systems biology of differentiation;406
21.6;19.6 Important tasks;407
21.7;19.7 Conclusion;408
21.8;References;409
22;Index;413

Gerhard Gross, Helmholtz Centre for Infection Research, Braunschweig, Germany; Thomas Häupl, Charité, Berlin, Germany.

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