Abstract
Summary
This report describes and evaluates cell therapy technologies and methods,
which have already started to play an important role in the practice of
medicine. Hematopoietic stem cell transplantation is replacing the old
fashioned bone marrow transplants. Role of cells in drug discovery is also
described. Cell therapy is bound to become a part of medical practice.
Stem cells are discussed in detail in one chapter. Some light is thrown on the
current controversy of embryonic sources of stem cells and comparison with
adult sources. Other sources of stem cells such as the placenta, cord blood
and fat removed by liposuction are also discussed. Stem cells can also be
genetically modified prior to transplantation.
Cell therapy technologies overlap with those of gene therapy, cancer vaccines,
drug delivery, tissue engineering and regenerative medicine. Pharmaceutical
applications of stem cells including those in drug discovery are also
described. Various types of cells used, methods of preparation and culture,
encapsulation and genetic engineering of cells are discussed. Sources of
cells, both human and animal (xenotransplantation) are discussed. Methods of
delivery of cell therapy range from injections to surgical implantation using
special devices.
Cell therapy has applications in a large number of disorders. The most
important are diseases of the nervous system and cancer which are the topics
for separate chapters. Other applications include cardiac disorders
(myocardial infarction and heart failure), diabetes mellitus, diseases of
bones and joints, genetic disorders, and wounds of the skin and soft tissues.
Regulatory and ethical issues involving cell therapy are important and are
discussed. Current political debate on the use of stem cells from embryonic
sources (hESCs) is also presented. Safety is an essential consideration of any
new therapy and regulations for cell therapy are those for biological
preparations.
The cell-based markets was analyzed for 2012, and projected to 2022.The
markets are analyzed according to therapeutic categories, technologies and
geographical areas. The largest expansion will be in diseases of the central
nervous system, cancer and cardiovascular disorders. Skin and soft tissue
repair as well as diabetes mellitus will be other major markets.
The number of companies involved in cell therapy has increased remarkably
during the past few years. More than 500 companies have been identified to be
involved in cell therapy and 286 of these are profiled in part II of the
report along with tabulation of 273 alliances. Of these companies, 156 are
involved in stem cells. Profiles of 71 academic institutions in the US
involved in cell therapy are also included in part II along with their
commercial collaborations. The text is supplemented with 55 Tables and 12
Figures. The bibliography contains 1,050 selected references, which are cited
in the text.
Table of Contents
Part I
0. Executive Summary 23
1. Introduction to Cell Therapy 27
- Introduction 27
- Historical landmarks of cell therapy 27
- Interrelationship of cell therapy technologies 29
- Cells and organ transplantation 29
- Cells and protein/gene therapy 30
- Cell therapy and regenerative medicine 31
- Cells therapy and tissue engineering 31
- Therapy based on cells involved in disease 32
- Advantages of therapeutic use of cells 32
- Cell-based drug delivery 33
- Cells as vehicles for gene delivery 33
- Red blood cells as vehicles for drug delivery 33
- Advantages of cell-based drug delivery 34
- Limitations of cell-based drug delivery 34
2. Cell Therapy Technologies 35
- Introduction 35
- Cell types used for therapy 35
- Sources of cells 35
- Xenografts 36
- Cell lines 36
- Immortalized cells 36
- Blood component therapy 36
- Therapeutic apheresis 36
- Leukoreduction 37
- Platelet therapy 37
- Basic technologies for cell therapy 38
- Cell culture 38
- Automated cell culture devices 38
- Cell culture for adoptive cell therapy 39
- Observation of stem cell growth and viability 39
- OpTmizer™ CTS™ T cell expansion tissue culture medium 39
- Companies involved in cell culture 39
- Cell sorting 41
- Flow cytometry 41
- Applications of flow cytometry 42
- A dielectrophoretic system for cell separation 42
- Adult stem cell sorting by identification of surface markers 42
- ALDESORTER system for isolation of stem cells 43
- Dynabead technology for cell sorting 43
- Elutra® Cell Separation System 43
- Molecular beacons for specific detection and isolation of stem cells
44
- Multitarget magnetic activated cell sorter 44
- Nanocytometry 44
- Scepter™ cytometer 45
- Companies supplying cell sorters 45
- Cell analysis 46
- Cell analyzers 46
- In vivo cell imaging 46
- Measuring cell density 47
- Single-cell gene expression analysis 47
- Preservation of cells 48
- Innovations in cryopreservation 48
- Packaging of cells 49
- Selective expansion of T cells for immunotherapy 49
- Cloning and cell therapy 50
- Techniques for cell manipulation 51
- Altering function of adult human cells 51
- Cell-based drug discovery 51
- Advantages and limitations of cell-based assays for drug discovery 51
- Advantages and limitations of cell-based toxicity screening 52
- Quality control of cells for drug discovery 52
- Companies involved in cell-based drug discovery 52
- Drug delivery systems for cell therapy 54
- Intravenous delivery of stem cells 55
- Intraarterial delivery of stem cells 55
- Pharmacologically active microcarriers 55
- Targeted delivery of engineered cells to specific tissues via circulation
56
- Devices for delivery of cell therapy 56
- Artificial cells 57
- Applications of artificial cells 57
- Cell encapsulation 57
- Diffusion capsule for cells 58
- Encapsulated cell biodelivery 58
- Therapeutic applications of encapsulated cells 58
- Nitric oxide delivery by encapsulated cells 60
- Implantation of microencapulated genetically modified cells 60
- Ferrofluid microcapsules for tracking with MRI 61
- Companies involved in encapsulated cell technology 61
- Electroporation 62
- Gene therapy 62
- Cell-mediated gene therapy 63
- Fibroblasts 63
- Chondrocyte 64
- Skeletal muscle cells 64
- Vascular smooth muscle cells 65
- Keratinocytes 65
- Hepatocytes 65
- Lymphocytes 65
- Mammalian artificial chromosomes 66
- In vivo tracking of cells 66
- Molecular imaging for tracking cells 66
- MRI technologies for tracking cells 67
- Superparamagnetic iron oxide nanoparticles as MRI contrast agents 68
- Visualization of gene expression in vivo by MRI 68
- Role of nanobiotechnology in development of cell therapy 68
- Cell transplantation for development of organs 69
- Cells transplantation and tolerance 69
- Strategies to improve tolerance of transplanted cells 70
- Encapsulation to prevent immune rejection 70
- Prevention of rejection of xenotransplants 70
- Expansion of allospecific regulatory T cells 71
- Removal and replacement of pathogenic cells of the body 71
- Therapeutic leukocytapheresis 71
3. Stem Cells 73
- Introduction 73
- Biology of stem cells 74
- Embryonic stem cells 74
- Growth and differentiation of ESCs 74
- Mechanisms of differentiation of ESCs 75
- Chemical regulation of stem cell differentiation 75
- In vitro differentiation of hESCs 75
- SIRT1 regulation during stem cell differentiation 75
- Regulation of stem cell self-renewal and differentiation 76
- hESCs for reprogramming human somatic nuclei 76
- Stem cells differentiation in the pituitary gland 76
- Influence of microenvironment on ESCs 77
- Role of genes in differentiation of ESCs 77
- Global transcription in pluripotent ESCs 77
- Role of p53 tumor suppressor gene in stem cell differentiation 78
- Role of Pax3 gene in stem cell differentiation 78
- Signaling pathways and ESC genes 78
- Epigenetics of hESCs 79
- Chromatin as gene regulator for ESC development 79
- Mechanism of regulation of stem cells for regeneration of body tissues
80
- Role of microenvironments in the regulation of stem cells 80
- Regulation and regeneration of intestinal stem cells 80
- Parthenogenesis and human stem cells 81
- Uniparental ESCs 82
- Bone marrow stem cells 82
- Hematopoietic stem cells 82
- Role of HSCs in the immune system 84
- Derivation of HSCs from ESCs 85
- Mesenchymal stem cells 85
- Multipotent adult progenitor cells 87
- Side population (SP) stem cells 87
- Differentiation of adult stem cells 87
- Growth and differentiation of HSCs 88
- Signaling pathways in the growth and differentiation of HSCs 88
- Mathematical modeling of differentiation of HSCs 89
- Role of prions in self renewal of HSCs 89
- Sources of stem cells 90
- Sources of of human embryonic stem cells 90
- Nuclear transfer to obtain hESCs 90
- Direct derivation of hESCs from embryos without nuclear transfer 91
- Alternative methods of obtaining hESCs 92
- Establishing hESC lines without destruction of embryo 92
- Altered nuclear transfer 93
- Small embryonic-like stem cells (SEL-SCs) 93
- Advantages and disadvantages of ESCs for transplantation 93
- Use of ESC cultures as an alternative source of tissue for transplantation
94
- Spermatogonial stem cells 95
- Amniotic fluid as a source of stem cells 95
- Amniotic fluid stem cells for tissue repair and regeneration 96
- Generation of iPS cells from AF cells 96
- Placenta as source of stem cells 97
- Amnion-derived multipotent progenitor cells 97
- Placenta as a source of HSCs 97
- Umbilical cord as a source of MSCs 98
- Umbilical cord blood as source of neonatal stem cells 98
- Cryopreservation of UCB stem cells 99
- UCB as source of MSCs 99
- Applications of UCB 100
- Advantages of UCB 100
- Limitations of the use of UCB and measures to address them 101
- Licensing and patent disputes involving UCB 102
- Infections following UCB transplants 102
- Unanswered questions about UCB transplantation 102
- Companies involved in UCB banking 103
- UCB banking in the UK 104
- US national UCB banking system 105
- Future prospects of UCB as a source of stem cells 106
- Induced pluripotent stem cells derived from human somatic cells 106
- Characteristics of iPSCs 107
- DNA methylation patterns of iPS cells 107
- iPSCs derived from oocytes through SCNT 107
- iPSCs derived from skin 108
- iPSCs derived from blood 108
- Use of retroviral vectors for generation of iPSCs 109
- Use of non-integrating viral vectors for generation of iPSCs 109
- Companies providing iPSCs 110
- Generation of clinically relevant iPSCs 110
- Generation of RBCs from iPSCs 111
- iPSCs and disease modeling 112
- iPSCs for patient-specific regenerative medicine 112
- Concluding remarks about clinical potential of iPSCs 113
- Induced conditional self-renewing progenitor cells 113
- Epiblast stem cells 114
- Comparison of development of human and mouse ESCs 114
- Conversion of hESCs to mouse ESC-like naïve states 114
- Sources of adult human stem cells 115
- Adipose tissue as a source of stem cells 115
- Intravenous infusion of adipose tissue derived MSCs 115
- iPSCs derived from adult human adipose stem cells 116
- Regulation of adipose stem cells differentiation 116
- Transforming adult adipose stem cells into other cells 116
- Multipotent stem-like cells derived from vascular endothelial cells
117
- Skin as a source of stem cells 117
- Controlling the maturation of embryonic skin stem cells 117
- Epidermal neural crest stem cells 117
- Follicle stem cells 118
- Mesenchymal stem cells in skin 118
- Regulation of stem cells in hair follicles 119
- Skin-derived precursor cells 119
- Stem cells in teeth 119
- Peripheral blood stem cells 120
- Spleen as a source of adult stem cells 120
- Search for master stem cells 121
- Vascular cell platform to self-renew adult HSC 121
- Adult stem cells vs embryonic stem cells 122
- Biological differences between adult and embryonic stem cells 122
- Neural crest stem cells from adult hair follicles 122
- Transdifferentiation potential of adult stem cells 122
- Limitations of adult stem cells 124
- Comparison of human stem cells according to derivation 124
- VENT cells 124
- Stem cell banking 125
- Stem cell technologies 125
- Analysis of stem cell growth and differentiation 125
- Activation of bone marrow stem cells into therapeutic cells 126
- Role of nitric oxide in stem cell mobilization and differentiation
126
- Role of natriuretic peptide receptor-C in self-renewal of murine ESCs
126
- Stem cell biomarkers 127
- Endoglin as a functional biomarker of HSCs 127
- STEMPRO® EZChek™ for analysis of biomarkers of hESCs 127
- SSEA-4 as biomarker of MSCs 127
- p75NTR as a biomarker to isolate adipose tissue-derived stem cells 128
- Neural stem cell biomarker 128
- Protein expression profile as biomarker of stem cells 128
- Real-time PCR for quantification of protein biomarkers 129
- Study of stem cell pathways 129
- Stem cell genomics 129
- Gene expression in hESCs 129
- Genomic alterations in cultured hESCs 130
- Study of transcriptional regulation of stem cell genes 130
- Casanova gene in zebrafish 131
- Nanog gene 131
- Gene inactivation to study hESCs 132
- RNAi to study gene inactivation in hESCs 132
- Study of ESC development by inducible RNAi 133
- Targeting Induced Local Lesions in Genomes 133
- Homologous recombination of ESCs 133
- Gene modification in genomes of hESCs and hiPSCs using zinc-finger
nuclease 134
- miRNA and stem cells 134
- Role of miRNAs in gene regulation during stem cell differentiation 134
- Influence of miRNA on stem cell formation and maintenance 135
- Transcriptional regulators of ESCs control miRNA gene expression 136
- Stem cells and cloning 136
- Cell nuclear replacement and cloning 136
- Nuclear transfer and ESCs 136
- Cloning from differentiated cells 138
- Cloning mice from adult stem cells 138
- Creating interspecies stem cells 139
- Cloned cells for transplantation medicine 139
- Claims of cloning of hESCs 139
- hESCs derived by SCNT 141
- Cytogenetics of embryonic stem cells 141
- Stem cell proteomics 142
- Comparative proteomic analysis of somatic cells, iPSCs and ESCs 142
- hESC phosphoproteome 143
- Proteomic studies of mesenchymal stem cells 143
- Proteomic profiling of neural stem cells 143
- Proteome Biology of Stem Cells Initiative 144
- Technologies for mobilization, expansion, and engraftment of stem cells
144
- Chemoattraction of neuronal stem cells through GABA receptor 145
- Enhancement of HSC engraftment by calcium-sensing receptor 145
- Ex vivo expansion of human HSCs in culture 145
- Ex vivo expansion of MSCs 146
- Ex vivo expansion of UCB cells for transplantation 146
- Expansion of adult stem cells by activation of Oct4 147
- Expansion of transduced HSCs in vivo 147
- Expansion of stem cells in vivo by Notch receptor ligands 147
- In vivo adipogenesis induced by adipose tissue-derived stem cells 148
- Selective mobilization of progenitor cells from bone marrow 148
- Selective Amplification 148
- Synthetic substrates for ESC growth and expansion 149
- Technologies for inducing differentiation of stem cells 149
- Enhancement of stem cell differentiation by Homspera 149
- Generation of RBCs from HSCs 149
- Generation of multiple types of WBCs from hESCs and iPSCs 150
- Growth factor-induced differentiation of MAPCs 150
- Lineage selection to induce differentiation of hESCs 150
- Mechanical strain to induce MSC differentiation 151
- Neurotrophin-mediated survival and differentiation of hESCs 151
- Synthetic biology and stem cells 151
- Use of RNAi to expand the plasticity of autologous adult stem cells
152
- Use of carbohydrate molecules to induce differentiation of stem cells
152
- Limitations of the currently available stem cell lines in the US 152
- Stem cell separation 153
- Stem cell culture 153
- Culture of hMSCs 154
- Elimination of contaminating material in stem cell culture 154
- Long-term maintenance of MSC multipotency in culture 156
- Nanofiber scaffolds for stem cell culture 156
- Conversion of stem cells to functioning adipocytes 157
- Mass production of ESCs 157
- Promoting survival of dissociated hESCs 157
- Analysis and characterization of stem cells 158
- Havesting and identification of EPCs 158
- Labeling of stem cells 158
- Labeling, imaging and tracking of stem cells in vivo 159
- Perfluorocarbon nanoparticles to track therapeutic cells in vivo 159
- PET imaging for tracking of stem cells 159
- Project for imaging in stem cell therapy research 159
- Quantum dots for labeling and imaging of stem cells 160
- Radiolabeling of MSCs for in vivo tracking 160
- Superparamagnetic iron oxide nanoparticles for tracking MSCs 161
- Tracking of transplanted muscle stem cells 161
- Applications of stem cells 161
- Commercial development and applications of adult stem cells 162
- Retrodifferentiation of stem cells 162
- MultiStem 162
- Controlling the maintenance process of hematopoietic stem cells 163
- Self renewal and proliferation of HSCs 163
- Aging and rejuvenation of HSCs 163
- Aging and MSCs 163
- Peripheral blood stem cell transplantation 164
- Role of stem cells in regeneration 164
- Promotion of regeneration by Wnt/beta-catenin signaling 165
- Stem cell activation for regeneration by using glucocortoids 165
- Stem cells and human reproduction 165
- Expansion of spermatogonial stem cells 165
- Conversion of ESCs into spermatogonial stem cells 166
- Conversion of stem cells to oocytes 166
- ESCs for treatment of infertility in women 166
- Cloning human embryos from oocytes matured in the laboratory 167
- In utero stem cell transplantation 167
- Innovations in delivery of stem cells 168
- Polymeric capsules for stem cell delivery 169
- Immunological aspects of hESC transplantation 169
- Immunosuppression to prevent rejection of hESC transplants 169
- Histocompatibility of hESCs 169
- Strategies for promoting immune tolerance of hESCs 170
- Stem cells for organ vascularization 171
- Activation of EphB4 to enhance angiogenesis by EPCs 171
- Advantages and limitations of clinical applications of iPSCs 172
- Advantages and limitations of clinical applications of MSCs 172
- Biofusion by genetically engineering stem cells 172
- Stem cell gene therapy 173
- Combination of gene therapy with nuclear transfer 173
- Gene delivery to stem cells by artificial chromosome expression 173
- Genetic manipulation of ESCs 173
- Genetic engineering of human stem cells for enhancing angiogenesis 174
- HSCs for gene therapy 174
- iPSCs for targeted gene correction of α1-antitrypsin deficiency
175
- Helper-dependent adenoviral vectors for gene transfer in ESCs 175
- Lentiviral vectors for in vivo gene transfer to stem cells 176
- Linker based sperm-mediated gene transfer technology 176
- Mesenchymal stem cells for gene therapy 176
- Microporation for transfection of MSCs 176
- Regulation of gene expression for SC-based gene therapy 177
- Stem cells and in utero gene therapy 177
- Therapeutic applications for hematopoietic stem cell gene transfer 177
- The future of hematopoietic stem cell gene therapy 178
- Stem cell pharmaceutics 178
- Pharmaceutical manipulation of stem cells 178
- Antisense approach for preservation and expansion of stem cells 179
- Expansion of HSCs in culture by inhibiting aldehyde dehydrogenase 180
- Manipulation of stem cells with growth factors 180
- Mobilization of stem cells by cytokines/chemokines 182
- Mobilization of adult human HSCs by use of inhibitors 183
- Mobilization of stem cells by HYC750 184
- Mobilization of stem cells by hyperbaric oxygen 184
- Mobilization by adenoviral vectors expressing angiogenic factors 184
- Stem cell mobilization by acetylcholine receptor agonists 185
- Use of parathyroid hormone to increase HSC mobilization 185
- Use of small molecule compounds for expansion of HSCs 185
- Role of stem cells in therapeutic effects of drugs 186
- Stem cells for drug discovery 186
- Target identification 186
- High-throughput screening 186
- Cardiomyocytes derived from hESCs 187
- ESCs as source of models for drug discovery 188
- hESC-derived hepatocytes for drug discovery 188
- Advantages and limitations of use of stem cells for drug discovery 189
- Stem cells for drug delivery 190
- Toxicology and drug safety studies using ESCs versus other cells 190
- Future challenges for stem cell technologies 192
- Generation of patient-specific pluripotent stem cells 192
- Hybrid embryos/cybrids for stem cell research 193
- In vivo study of human hemopoietic stem cells 194
- Markers for characterizing hESC lines 194
- MBD3-deficient ESC line 194
- Research into plasticity of stem cells from adults 195
- Stem cell biology and cancer 195
- Stem cells and aging 196
- Stem cells in space 197
- Study of the molecular mechanism of cell differentiation 197
- Switch of stem-cell function from activators to repressors 198
- Stem cell research at academic centers 198
- International Regulome Consortium 199
- Companies involved in stem cell technologies 200
- Concluding remarks about stem cells 205
- Challenges and future prospects of stem cell research 205
4. Clinical Applications of Cell Therapy 207
- Introduction 207
- Cell therapy for hematological disorders 207
- Transplantation of autologous hematopoietic stem cells 207
- Hemophilias 207
- Ex vivo cell/gene therapy of hemophilia B 208
- Cell/gene therapy of hemophilia A 208
- Hematopoietic stem cell therapy for thrombocytopenia 209
- Stem cell transplant for sickle cell anemia 209
- Treatment of chronic acquired anemias 210
- Implantation of genetically engineered HSCs to deliver rhEpo 210
- Drugs acting on stem cells for treatment of anemia 210
- Stem cell therapy of hemoglobinopathies 211
- Stem cells for treatment of immunoglobulin-light chain amyloidosis 211
- Future prospects of cell therapy of hematological disorders 211
- Cell therapy for immunological disorders 212
- Role of dendritic cells in the immune system 212
- Modifying immune responses of DCs by vaccination with lipiodol-siRNA
mixtures 212
- Potential of MSCs as therapy for immune-mediated diseases 213
- Stem cell therapy of chronic granulomatous disease 213
- Stem cell therapy of X-linked severe combined immunodeficiency 214
- Stem cell therapy of autoimmune disorders 214
- Treatment of rheumatoid arthritis with stem cells 214
- Treatment of Crohn's disease with stem cells 215
- Stem cell transplants for scleroderma 215
- Role of T Cells in immunological disorders 216
- Autologous T cells from adult stem cells 216
- Cell therapy for graft vs host disease 217
- MSCs for GVHD 218
- Cell therapy for viral infections 218
- T-cell therapy for CMV 218
- T-cell therapy for HIV infection 219
- T-cell immunity by Overlapping Peptide-pulsed Autologous Cells 219
- Anti-HIV ribozyme delivered in hematopoietic progenitor cells 220
- Dendritic-cell targeted DNA vaccine for HIV 220
- Cell therapy of lysosomal storage diseases 220
- Niemann-Pick disease 221
- Gaucher's disease 221
- Fabry's disease 222
- Cell therapy for diabetes mellitus 222
- Limitations of current treatment 223
- Limitations of insulin therapy for diabetes mellitus 223
- Limitations of pancreatic transplantation 224
- Islet cell transplantation 224
- Autologous pancreatic islet cell transplantation in chronic pancreatitis
224
- Clinical trials of pancreatic islet cell transplants for diabetes 224
- Drawbacks of islet cell therapy 225
- Use of an antioxidant peptide to improve islet cell transplantation
226
- Cdk-6 and cyclin D1 enhance human beta cell replication and function
226
- A device for delivery of therapeutic cells in diabetes 226
- Monitoring of islet cell transplants with MRI 227
- Concluding remarks about allogeneic islet transplantation for diabetes
227
- Encapsulation of insulin producing cells 227
- Encapsulated porcine pancreatic islet cells for pancreas 228
- Encapsulated insulinoma cells 228
- Magnetocapsule enables imaging/tracking of islet cell transplants 228
- Islet precursor cells 229
- Dedifferentiation of β cells to promote regeneration 229
- Pharmacological approaches for β cell regeneration 230
- Xenotransplantation of embryonic pancreatic tissue 231
- Non-pancreatic tissues for generation of insulin-producing cells 231
- Exploiting maternal microchimerism to treat diabetes in the child 231
- Bio-artificial substitutes for pancreas 232
- Role of stem cells in the treatment of diabetes 232
- Embryonic stem cells for diabetes 232
- HSC transplantation to supplement immunosuppressant therapy 233
- Human neural progenitor cells converted into insulin-producing cells
234
- Insulin-producing cells derived from UCB stem cells 234
- iPS cells for diabetes 235
- Isolation of islet progenitor cells 235
- Pancreatic progenitor cells Expansion in vitro 235
- Pancreatic stem cells 235
- Stem cell injection into portal vein of diabetic patients 236
- Dendritic cell-based therapy for type 1 diabetes 236
- Vaccine for diabetes 237
- Gene therapy in diabetes 237
- Viral vectors for gene therapy of diabetes 237
- Genetically engineered dendritic cells 238
- Genetically altered liver cells 238
- Genetically modified stem cells 238
- Companies developing cell therapy for diabetes 238
- Concluding remarks about cell and gene therapy of diabetes 239
- Cell therapy of gastrointestinal disorders 241
- Inflammatory bowel disease 241
- Cell therapy for liver disorders 241
- Types of cells used for hepatic disorders 242
- Methods of delivery of cells for hepatic disorders 242
- Bioartificial liver 242
- Hepatocyte-based artificial liver 242
- Extracorporeal Liver Assist Device 243
- Limitations of bioartificial liver 243
- Proliferating cell-based bioartificial liver 243
- Stem cells for hepatic disorders 244
- Deriving hepatocytes from commercially available hMSCs 244
- Implantation of hepatic cells derived from hMSCs of adipose tissue 245
- Heterologous adult liver progenitor cells 245
- Liver stem cell culture 245
- MSC derived molecules for reversing hepatic failure 246
- Cell-based gene therapy for liver disorders 246
- Transplantation of genetically modified fibroblasts 246
- Transplantation of genetically modified hepatocytes 247
- Genetically modified hematopoietic stem cells 247
- iPSCs derived from somatic cells for liver regeneration 247
- Hepatocyte-like cells derived from human parthenogenetic stem cells 248
- Clinical applications 248
- Future prospects of cell-based therapy of hepatic disorders 249
- Cell therapy of renal disorders 249
- Bioartificial kidney 250
- Cell-based repair for vascular access failure in renal disease 250
- Mesangial cell therapy for glomerular disease 250
- Stem cells for renal disease 251
- Role of stem cells in renal repair 251
- Bone marrow stem cells for renal disease 251
- Human amniotic fluid stem cells for renal regeneration 252
- MSC therapy for renal disease 252
- Cell therapy for pulmonary disorders 252
- Delivery of cell therapy for pumonary disorders 252
- Intratracheal injection of cells for pulmonary hypoplasia 253
- Role of stem cells in pulmonary disorders 253
- Lung stem cells 253
- Lung tissue regeneration from stem cells 253
- Role of stem cells in construction of the Cyberlung 254
- Respiratory epithelial cells derived from UCB stem cells 254
- Respiratory epithelial cells derived from hESCs 254
- Lung tissue engineering with adipose stromal cells 255
- Cell-based tissue-engineering of airway 255
- Pulmonary disorders that can be treatable with stem cells 256
- Acute lung injury and ARDS treated with MSCs 256
- Bronchopulmonary dysplasia treated with MSCs 257
- Chronic obstructive pulmonary disease treated with MSCs 257
- Cystic fibrosis treatment with genetically engineered MSCs 258
- Lung regeneration by integrin α6β4-expressing alveolar
epithelial cell 258
- Pulmonary arterial hypertension treatment with EPCs 258
- Cell therapy for disorders of bones and joints 259
- Repair of fractures and bone defects 259
- Adult stem cells for bone grafting 260
- Bone regeneration by human very small embryonic-like (hVSEL) cells 260
- Cell therapy for osteonecrosis 260
- Cell therapy for radionecrosis 261
- Cell therapy for cervical vertebral interbody fusion 261
- Cell-mediated gene therapy for bone regeneration 261
- ESCs for bone repair 262
- hiPSCs for engineering personalized bone grafts 262
- Intrauterine use of MSCs for osteogenesis imperfecta 262
- In vivo bone engineering as an alternative to cell transplantation 262
- In vivo differentiation of pluripotent stem cells for bone regeneration
263
- MSCs for repair of bone defects 263
- MSCs for repair of bone fractures 265
- Osteocel 266
- Stem cells for repairing skull defects 266
- Stem cell-based bone tissue engineering 267
- Spinal fusion using stem cell-based bone grafts 268
- Osteoarthritis and other injuries to the joints 268
- Mosaicplasty 269
- Autologous cultured chondrocytes 269
- Autologous intervertebral disc chondrocyte transplantation 270
- Cartilage repair by genetically modified fibroblasts expressing TGF-β
271
- Cartilage generation from stem cells 271
- Cartilage engineering from iPSCs 273
- Repair of osteonecrosis by bone marrow derived MSCs 273
- Role of cell therapy in repair of knee cartilage injuries 273
- Role of cells in the repair of anterior cruciate ligament injury 275
- Autologous tenocyte implantation in rotator cuff injury repair 276
- Platelet injection for tennis elbow 276
- Cell therapy of rheumatoid arthritis 276
- Cell therapy for diseases of the eye 277
- Cell therapy for corneal repair 277
- Stem cell therapy for limbal stem cell deficiency 279
- Role of stem cells in fibrosis following eye injury 279
- Stem cell transplantation for radiation sickness 279
- MSCs for treatment of radiation damage to the bone 279
- MSCs for regeneration of ovaries following radiotherapy damage 280
- Cell therapy for wound healing 280
- Cells to form skin substitutes for healing ulcers 281
- CellSpray for wound repair 281
- Cell therapy for burns 282
- Closure of incisions with laser guns and cells 283
- Genetically engineered keratinocytes for wound repair 283
- Stem cells for skin regeneration 283
- Follicular stem cells for skin and wound repair 283
- MSCs for wound healing 284
- Regeneration of aging skin by adipose-derived stem cells 284
- Reprogramming autologous stem cells for wound regeneration 284
- Role of amniotic fluid MSCs in repair of fetal wounds 285
- Concluding remarks on regeneration of skin by stem cells 285
- Cell therapy for regeneration 285
- Stem cells for regenerating organs 285
- Umbilical cord blood for regeneration 286
- Role of stem cells in regeneration of esophageal epithelium 287
- Cell therapy for regeneration of muscle wasting 287
- Role of cells in tissue engineering and reconstructive surgery 288
- Scaffolds for tissue engineering 288
- Improving vascularization of engineered tissues 288
- Repair of aging skin by injecting autologous fibroblasts 288
- Enhancing vascularization by combining cell and gene therapy 289
- Nanobiotechnology applied to cells for tissue engineering 289
- Choosing cells for tissue engineering 290
- Stem cells for tissue repair 290
- ESCs vs adult SCs for tissue engineering 291
- Use of adult MSCs for tissue engineering 291
- Stem cells for tissue engineering of various organs 292
- Breast reconstruction by adipose tissue-derived stem cells 292
- Engineering of healthy living teeth from stem cells 292
- Intra-uterine repair of congenital defects using amniotic fluid MSCs
293
- Skin regeneration by stem cells as an alternative to face transplant
294
- Tissue engineering of bone by stem cells 294
- Cell-based tissue engineering in genitourinary system 295
- Urinary incontinence 295
- Tissue engineering of urinary bladder 296
- Label retaining urothelial cells for bladder repair 297
- MSCs for bladder repair 297
- Tissue-engineering of urethra using autologous cells 297
- Repair of the pelvic floor with stem cells from the uterus 298
- Reconstruction of vagina from stem cells 298
- Reconstruction of cartilage for repair of craniofacial defects 298
- Intraoperative cell therapy 298
- Cell therapy for rejuvenation 299
- Cell therapy for performance enhancement in sports 299
- Application of stem cells in veterinary medicine 300
- Use of stem cells to repair tendon injuries 300
- Stem cells for spinal cord injury in dogs 300
5. Cell Therapy for Cardiovascular Disorders 303
- Introduction to cardiovascular disorders 303
- Limitations of current therapies for myocardial ischemic disease 303
- Types of cell therapy for cardiovascular disorders 303
- Cell-mediated immune modulation for chronic heart disease 305
- Human cardiovascular progenitor cells 305
- Inducing the proliferation of cardiomyocytes 306
- Pericardial origin of colony-forming units 306
- Role of the SDF-1-CXCR4 axis in stem cell therapies for myocardial
ischemia 307
- Role of splenic myocytes in repair of the injured heart 307
- Reprogramming of fibroblasts into functional cardiomyocytes 307
- Small molecules to enhance myocardial repair by stem cells 308
- Cell therapy for atherosclerotic coronary artery disease 308
- MyoCell™ (Bioheart) 308
- Cardiac stem cells 309
- Cardiomyocytes derived from epicardium 310
- Methods of delivery of cells to the heart 310
- Cellular cardiomyoplasty 310
- IGF-1 delivery by nanofibers to improve cell therapy for MI 311
- Non-invasive delivery of cells to the heart by Morph®guide catheter
311
- Cell therapy for cardiac revascularization 311
- Transplantation of cardiac progenitor cells for revascularization of
myocardium 311
- Stem cells to prevent restenosis after coronary angioplasty 312
- Role of cells in cardiac tissue repair 313
- Modulation of cardiac macrophages for repair of infarct 313
- Transplantation of myoblasts for myocardial infarction 313
- Patching myocardial infarction with fibroblast culture 314
- Cardiac repair with myoendothelial cells from skeletal muscle 314
- Myocardial tissue engineering 314
- Role of stem cells in repair of the heart 315
- Role of stem cells in cardiac regeneration following injury 315
- Cardiomyocytes derived from adult skin cells 316
- Cardiomyocytes derived from ESCs 316
- Cardiomyocyte differentiation from hIPSCs 318
- Studies to identify subsets of progenitor cells suitable for cardiac
repair 318
- Technologies for preparation of stem cells for cardiovascular therapy
318
- Pravastatin for expansion of endogenous progenitor and stem cells 318
- Cytokine preconditioning of human fetal liver CD133+ SCs 319
- Expansion of adult cardiac stem cells for transplantation 319
- Role of MSCs in growth of CSCs 320
- Role of ESCs in repair of the heart 320
- ESC transplantation for tumor-free repair of the heart 321
- Transplantation of stem cells for myocardial infarction 321
- Autologous bone marrow-derived stem cell therapeutics 321
- Autologous bone marrow-derived mesenchymal precursor stem cells 322
- Intracoronary infusion of mobilized peripheral blood stem cells 322
- Transplantation of cord blood stem cells 323
- Transplantation of hESCs 323
- Transplantation of HSCs 323
- Transplantation of autologous angiogenic cell precursors 324
- Transplantation of adipose-derived stem cells 324
- Transplantation of bone marrow-derived cells for myocardial infarct
325
- Transplantation of human umbilical cord perivascular cells 326
- Transplantation of endothelial cells 326
- Transplantation of cardiomyocytes differentiated from hESCs 327
- Stem cell therapy for cardiac regeneration 327
- Regeneration of the chronic myocardial infarcts by HSC therapy 327
- Human mesenchymal stem cells for cardiac regeneration 328
- In vivo tracking of MSCs transplanted in the heart 329
- MSCs for hibernating myocardium 329
- Simultaneous transplantation of MSCs and skeletal myoblasts 330
- Transplantation of genetically modified cells 330
- Transplantation of genetically modified MSCs 330
- Transplantation of cells secreting vascular endothelial growth factor
330
- Transplantation of genetically modified bone marrow stem cells 330
- Cell transplantation for congestive heart failure 330
- AngioCell gene therapy for congestive heart failure 331
- Injection of adult stem cells for CHF 332
- Intracoronary infusion of cardiac stem cells 332
- Myoblasts for treatment of congestive heart failure 333
- Stem cell therapy for dilated cardiac myopathy 333
- Role of cell therapy in cardiac arrhythmias 333
- Atrioventricular conduction block 334
- Genetically engineered cells as biological pacemakers 334
- Ventricular tachycardia 335
- Prevention of myoblast-induced arrhythmias by genetic engineering 335
- ESCs for correction of congenital heart defects 336
- Cardiac progenitors cells for treatment of heart disease 336
- Autologus stem cells for chronic myocardial ischemia 337
- Role of cells in cardiovascular tissue engineering 337
- Construction of blood vessels with cells 337
- Engineered arteries for bypass grafts 338
- Fetal cardiomyocytes seeding in tissue-engineered cardiac grafts 338
- Targeted delivery of endothelial progenitor cells labeled with
nanoparticles 338
- UCB progenitor cells for engineering heart valves 338
- Cell-based in vitro regeneration of heart for transplantation 339
- Cell therapy for peripheral vascular disease 339
- ALD-301 339
- Cell/gene therapy for PVD 340
- Cell therapy for CLI in diabetics 340
- Colony stimulating factors for enhancing peripheral blood stem cells
340
- Intramuscular autologous bone marrow cells 341
- Ixmyelocel-T cell therapy for critical limb ischemia 341
- Stem cell-coated vascular grafts for femoral-tibial arterial bypass
341
- Clinical trials of cell therapy in cardiovascular disease 342
- Mechanism of the benefit of cell therapy for heart disease 344
- A critical evaluation of cell therapy for heart disease 344
- Publications of clinical trials of cell therapy for CVD 345
- Current status of cell therapy for cardiovascular disease 345
- Future directions for cell therapy of CVD 346
- Prospects of adult stem cell therapy for repair of heart 346
- Combination of cells with biomedical scaffolds 347
- Regeneration of cardiomyocytes without use of cardiac stem cells 347
6. Cell Therapy for Cancer 349
- Introduction 349
- Cell therapy technologies for cancer 349
- Cell-based delivery of anticancer therapy 350
- Cellular immunotherapy for cancer 350
- Treatments for cancer by ex vivo mobilization of immune cells 351
- Granulocytes as anticancer agents 352
- Neutrophil granulocytes in antibody-based immunotherapy of cancer 352
- Cancer vaccines 352
- Autologous tumor cell vaccines 352
- BIOVAXID 353
- OncoVAX 353
- Tumor cells treated with dinitrophenyl 353
- Vaccines that simultaneously target different cancer antigens 353
- Gene modified cancer cells vaccines 354
- GVAX cancer vaccines 354
- K562/GM-CSF 354
- Active immunotherapy based on antigen specific to the tumor 355
- The use of dendritic cells for cancer vaccination 355
- Autologous dendritic cells loaded ex vivo with telomerase mRNA 355
- Dendritic cell-targeted protein vaccines 356
- Dendritic/tumor cell fusion 356
- Genetically modified dendritic cells 357
- In vivo manipulation of dendritic cells 357
- Preclinical and clinical studies with DC vaccines 357
- Vaccines based on dendritic cell-derived exosomes 358
- Limitations of DC vaccines for cancer 358
- Future developments to enhance clinical efficacy of DC vaccines 358
- Lymphocyte-based cancer therapies 360
- Adoptive cell therapy 360
- Chimeric antigen receptor T cells 361
- Combination of antiangiogenic agents with ACT 363
- Expansion of antigen-specific cytotoxic T lymphocytes 363
- Genetic engineering of tumor cells to activate T helper cells 363
- Rescue of CD8+ T cells for use in tumor immunotherapy 364
- Tumor infiltrating lymphocytes 364
- Hybrid cell vaccination 364
- Chemoimmunotherapy 365
- Stem cell-based anticancer therapies 365
- Stem cell transplantation in cancer 365
- Peripheral blood stem cell transplantation 365
- Stem cell transplantation for hematological malignancies 368
- Long-term results of HSC transplantation 369
- Prediction of T-cell reconstitution after HSC transplantation. 369
- HSC transplantation followed by GM-CSF-secreting cell vaccines 369
- HSC transplantation for renal cell cancer 370
- Complications of stem cell transplants in cancer 370
- Graft-versus-host disease (GVHD) 370
- Delayed immune reconstitution leading to viral infections and relapse
371
- Tumor cell contamination 371
- Neurological complications 371
- Hepatic veno-occlusive disease 371
- Current status of the safety of allogeneic HSC transplantation 372
- Complications of PBSC transplantation in children 372
- Role of MSCs in cancer 373
- MSC-mediated delivery of anticancer therapeutics 373
- Nonmyeloablative allogeneic hematopoietic stem cell transplantation
373
- Umbilical cord blood transplant for leukemia 374
- hESC-derived NK cells for treatment of cancer 375
- ESC vaccine for prevention of lung cancer 375
- Genetic modification of stem cells for cancer therapy 375
- Genetic modification of hematopoietic stem cells 375
- Use of hematopoietic stem cells to deliver suicide genes to tumors 376
- Delivery of anticancer agents by genetically engineered MSCs 376
- Mesenchymal progenitor cells for delivery of oncolytic adenoviruses
377
- Genetically modified NSCs for treatment of neuroblastoma 377
- Innovations in cell-based therapy of cancer 378
- Use of immortalized cells 378
- Cancer therapy based on natural killer cells 378
- Cytokine-induced killer cells 378
- Mesothelin as a target for cancer immunotherapy 378
- Nanomagnets for targeted cell-based cancer gene therapy 379
- Implantation of genetically modified encapsulated cells for anticancer
therapy 379
- Antiangiogenesis therapy by implantation of microencapsulated cells 379
- Recombinant tumor cells secreting fusion protein 379
- NovaCaps®, for pancreatic cancer 380
- A device for filtering cancer and stem cells in the blood 380
- Cancer stem cells 380
- Role of integrative nuclear signaling in stem cell development 381
- Cancer stem cell markers 381
- Breast cancer stem cells 381
- Role of intestinal stem cells in intestinal polyposis 382
- Role of endothelial progenitor cells in tumor angiogenesis 382
- Role of cancer stem cells in metastases 383
- Therapeutic implications of cancer stem cells 383
- Targeting cancer stem cells in leukemia 384
- Targeting stem cells in ovarian cancer 384
- Targeting cancer stem cells to screen anticancer drugs 385
- Companies involved in cell-based cancer therapy 385
- American Association for Cancer Research and ESCs 386
- Future of cell-based immunotherapy for cancer 387
7. Cell Therapy for Neurological Disorders 389
- Introduction 389
- Regeneration of the nervous system by endogenous stem cells 389
- Molecular mechanism of neurogenesis 389
- Generation of neurons from astroglia 390
- In vivo cell replacement therapy by locally induced neural progenitor
cells 390
- Types of cells used for treatment of neurological disorders 391
- Activated T lymphocytes 391
- Differentiation of placenta-derived multipotent cells into neurons 391
- Mesenchymal stem cells induced to secrete neurotrophic factors 392
- Neural stem cells 392
- Development of human CNS stem cells 392
- Distinction between NSCs and intermediate neural progenitors 393
- Embryonic stem cell-derived neurogenesis 393
- Fusion of NSCs with endogenous neurons 394
- Induction of NSCs from hESCs 394
- Mechanism of migration of NSCs to sites of CNS injury 395
- Monitoring of implanted NSCs labeled with nanoparticles 396
- Neural progenitor cells 396
- Neural stem cells as therapeutic delivery vehicles 398
- Neural stem cells in the subventricular zone of the brain 398
- Oligodendrocyte progenitor cells 398
- Promotion of neural stem cells expansion by betacellulin 398
- Proteomics of neural stem cells 399
- Regulation of neural stem cells in the brain 399
- Role of CSF proteins in regulation of neural progenitor cells 400
- Sequencing the transcriptomes of neural stem cells 401
- Study of neural differentiation of hESCs by NeuroStem Chip 401
- Transformation of neural stem cells into other cell types 401
- Use of epidermal neural crest stem cells for neurological disorders
401
- Stem cell transplantation in the CNS 402
- Development of CNS cells from non-CNS stem cells 402
- Expansion of adult human neural progenitors 403
- Hair-follicle stem cells for neural repair 403
- Neurospheres 403
- Stem cells from olfactory epithelium for transplantation in the CNS
404
- Stem cells from human umbilical cord blood for CNS disorders 404
- Choroid plexus cells for transplantation 404
- Dental pulp cells for neuroprotection 405
- Derivation of CNS cells from peripheral nervous system 405
- Fetal tissue transplants 405
- Immortalized cells for CNS disorders 406
- Laboratory mice with human brain cells 406
- Olfactory ensheathing cells for CNS repair 407
- Ideal cells for transplantation into the nervous system 407
- Cell therapy techniques for neurological applications 407
- Carbon nanotubes to aid stem cell therapy of neurological disorders
407
- Cells used for gene therapy of neurological disorders 408
- Fibroblasts 408
- Stem cells 408
- Neuronal cells 409
- Immortalized neural progenitor cells 409
- Astrocytes 409
- Cerebral endothelial cells 410
- Human retinal pigmented epithelial cells 410
- Enhancement of growth of stem cells in the brain by drugs 410
- C3-induced differentiation and migration of NPC for repair of the brain
411
- Stem cell therapies of neurological disorders combined with HBO 412
- hESCs for CNS repair 412
- Methods of delivery of cells to the CNS 413
- Engineered stem cells for drug delivery to the brain 413
- Neuronal differentiation of stem cells 413
- Stem cells preparations for CNS disorders 414
- Tracking of stem cells in the CNS by nanoparticles and MRI 415
- Use of neural stem cells to construct the blood brain barrier 415
- Encapsulated cells 416
- CNS neotissue implant 416
- Intrathecal delivery of stem cells 416
- CNS delivery of cells by catheters 417
- Intravascular administration 417
- Neurological disorders amenable to cell therapy 418
- Neuroprotection by cell therapy 418
- Cells secreting neuroprotective substances 418
- Stem cells for neuroprotection 419
- Neuroprotection by intravenous administration of HSCs 419
- Human UCB-derived stem cells for the aging brain 419
- hESC transplantation to prevent cognitive impairment from radiation 419
- Neurodegenerative disorders 420
- MSCs for therapy of neurodegenerative disorders 420
- Role of stem cells in neurodegenerative disorders 421
- Role of NSCs in disorders associated with aging brain 422
- NSCs for improving memory 422
- Parkinson's disease 423
- Cell therapies for PD 423
- Origin and fate of dopamine neurons 424
- Human dopaminergic neurons for PD 424
- Graft survival-enhancing drugs 425
- Xenografting porcine fetal neurons 425
- Encapsulated cells for PD 426
- Stem cell transplantation in animal models of PD 426
- Trials of stem cell transplantation in PD patients 428
- Stem cells for production of glial derived neurotrophic factor 429
- Potential of regeneration of endogenous stem cells in PD 429
- Human retinal pigment epithelium cells for PD 430
- Tumorigenic potential of transplantated dopaminergic hESCs 430
- Transplantation of embryonic medial ganglionic eminence cells 431
- Delivery of cells for PD 431
- MSCs for multiple system atrophy 431
- Cell therapy for Huntington's disease 432
- Fetal striatal cell transplantation 432
- Transplantation of encapsulated porcine choroids plexus cells 432
- iPSCs for HD 433
- Cell therapy for Alzheimer's disease 433
- Choroid plexus epithelial cells for AD 433
- Implantation of genetically engineered cells producing NGF 434
- Implantation of stem cells derived from the skin 434
- Neural stem cell implantation for Alzheimer's disease 434
- Cell therapy for amyotrophic lateral sclerosis 435
- Stem cell techniques for study of ALS 435
- Use of stem cells for ALS 436
- Transplantation of glial restricted precursors in ALS 437
- Stem cell-based drug discovery for ALS 438
- Cell therapy for demyelinating disorders 438
- Autologous bone marrow stem cell therapy for multiple sclerosis 439
- ESCs for remyelination 439
- Fusokine method of personalized cell therapy of MS 439
- Hematopoietic stem cell transplantation for MS 440
- Mechanism of repair of demyelination after NSC transplantation 440
- MSCs for multiple sclerosis 441
- Neural progenitor cells for neuroprotection in MS 441
- T cell-based personalized vaccine for MS 442
- Stem cells for chronic inflammatory demyelinating polyneuropathy 442
- Stem cell transplantation for Pelizaeus-Merzbacher disease 442
- X-linked adrenoleukodystrophy 442
- Cell therapy of stroke 443
- Adult stem cell therapy in stroke 443
- Implantation of genetically programmed ESCs 444
- Intravenous infusion of MSCs 444
- Intravenous infusion of human UCB stem cells 445
- Intracerebral administration of human adipose tissue stromal cells 446
- Neural stem cell therapy for stroke 446
- Transplantation of encapsulated porcine choroids plexus 447
- Transplantation of fetal porcine cells 447
- Role of cell therapy in management of stroke according to stage 448
- Clinical trials of cell therapy for stroke 448
- Future of cell therapy for stroke 449
- Cell therapy of traumatic brain injury 450
- Cell/gene therapy for TBI 451
- Clinical trials of autologous stem cell therapy for TBI 451
- Limitations of stem cell therapy for acute TBI 452
- Improving the microenvironments of transplanted cells in TBI 452
- Cell therapy for spinal cord injury 452
- Autoimmune T cells against CNS myelin-associated peptide 453
- Fetal neural grafts for SCI 453
- Olfactory-ensheathing cells for SCI 453
- Oligodendrocyte precursor cells for treatment of SCI 454
- Schwann cell transplants for SCI 454
- Transplantation of glial cells for SCI 454
- Stem cells for SCI 454
- Bone marrow stem cells for SCI 455
- Embryonic stem cells for SCI 455
- Transplantation of induced pluripotent stem cells in SCI 456
- Transplantation of MSCs for SCI 456
- Transplantation of NSCs for SCI 456
- Transplantation of human dental pulp stem cells 457
- Transdifferentiation of BM stem cells into cholinergic neurons for SCI
457
- Evaluation of experimental studies of stem cell transplantation in SCI
458
- Spinal stem cells for treatment of ischemic injury of spinal cord 458
- Combined approaches for regeneration in SCI 459
- Combined cell/gene therapy for SCI 459
- Delivery of cells in SCI 459
- Intrathecal injection of cells labeled with magnetic nanoparticles 460
- Intravenous injection of stem cells for spinal cord repair 460
- Clinical applications of stem cells for SCI 460
- Autologous bone marrow cell transplantation for SCI 460
- Cell therapy of syringomyelia 461
- Cell therapy for neurogenetic disorders 461
- Hurler's syndrome treated with stem cells 461
- Krabbe's disease treated with UCB stem cells 462
- Krabbe's disease treated with combination of cell and gene therapy 462
- Mitochondrial encephalomyopathies treated with stem cells 463
- Sanfilippo syndrome type B treated with UCB stem cells 463
- Cell therapy for lysosomal storage disorders 463
- Cell therapy for Batten disease 463
- Cell/gene therapy for Farber's disease 464
- Genetically modified HSCs for metachromatic leukodystrophy 464
- Neural stem cells for lysosomal storage disorders 465
- Cell therapy of epilepsy 465
- Cell therapy of posttraumatic epilepsy 465
- Cell therapy for temporal lobe epilepsy 466
- Cell therapy for pharmacoresistant epilepsies 466
- Cell therapy for developmental neurological disorders 467
- Cell therapy for cerebral palsy 467
- Cell-based therapies for malignant brain tumors 468
- Bone morphogenetic protein for inhibition of glioblastoma multiforme
468
- Dendritic cell therapy for brain tumors 468
- Encapsulated cells for brain tumors 469
- Immunotherapy of GBM targeting cancer stem cells 469
- Mesenchymal stem cells for the treatment of gliomas 470
- Neural stem cells for drug/gene delivery to brain tumors 470
- Role of cancer stem cells in resistance to radiotherapy 471
- Stem cell-based therapy targeting EGFR in GBM 472
- Targeting stem cells in brain tumors 472
- Clinical trials of cell therapy of glioblastoma multiforme 472
- Cell therapy for muscle disorders 473
- Duchenne muscular dystrophy 473
- Combination of cell and pharmacotherapy for DMD 473
- Myoblast transplant for DMD 474
- Myoblast-based gene transfer 474
- Myoblasts lacking the MyoD gene 474
- Myoblast injection for treatment of other muscular dystrophies 475
- Role of satellite cells in the treatment of DMD 475
- Stem cells for DMD 476
- Wnt7a treatment for DMD 477
- Cell therapy for autism 477
- Management of chronic intractable pain by cell therapy 478
- Implantation of chromaffin cells 478
- Role of stem cells in management of pain 479
- Implantation of astrocytes secreting enkephalin 479
- Cells for delivery of antinociceptive molecules 479
- Implantation of genetically engineered cells 480
- Cell therapy for low back pain 480
- Cell therapy for neuroendocrine disorders 480
- Pituitary stem cells 480
- Cell therapy for retinal degenerative disorders 481
- iPSCs for AMD 482
- Human retinal stem cells 482
- Delivery of CNTF by encapsulated cell intraocular implants 483
- Stem cell transplantation in the retina 483
- ESCs for retinal degenerative disorders 484
- hESC-derived RPE cells for macular dystrophy 484
- Neuroprotective effect of neural progenitor cell transplantation 484
- Genetically engineered retinal pigmented epithelial cell lines 484
- Combining cell and gene therapies for retinal disorders 485
- Stem cell therapy for hearing loss 485
- Cell thery for peripheral nerve lesions 486
- Cell transplants for peripheral nerve injuries 486
- Role of adipose-derived stem cells in peripheral nerve regeneration
486
- Treatment of diabetic neuropathy with endothelial progenitor cells 486
- Complications of cell therapy of neurological disorders 487
- Tumor formation after CNS transplantation of stem cells 487
- Uncontrolled differentiation of implanted cells 487
- Donor stem cell-derived brain tumor 487
- Tumorigenicity of ESC-derived retinal progenitor cells 487
- Clinical trials of cell therapy in neurological disorders 488
- Future prospects for cell therapy of CNS disorders 489
8. Ethical, Legal and Political Aspects of Cell therapy 491
- Introduction 491
- Political and ethical aspects of hESC research in the US 491
- Ethical issues concerning fetal tissues 491
- Morality and hESC research 491
- Opponents of hESC research in the US 492
- Use of hESCs in NIH-supported research 493
- Politics of hESC research in the US 494
- Public opinion in the US about hESC research 496
- Human stem cell cloning in the US 497
- Stem cell guidelines of various US institutions 498
- Ethics of transplanting human NSCs into the brains of nonhuman primates
498
- Stem cell lines available worldwide 499
- Stem cell policies around the world 500
- Countries with no defined policies on hESC research 500
- Australia 501
- Canada 501
- China 502
- Denmark 503
- France 503
- Germany 503
- India 505
- Ireland 506
- Israel 506
- Italy 506
- Japan 507
- The Netherlands 507
- Saudi Arabia 508
- Singapore 508
- South Africa 508
- South Korea 509
- Spain 509
- Sweden 509
- Switzerland 510
- United Kingdom 510
- UK StemCellBank 511
- European Union 512
- EU guidelines for stem cell research 512
- European stem cell bank 514
- EMBO's recommendations for stem cell research 514
- Public opinion in Europe about hESC research 515
- United Nations, cloning and nuclear transfer 516
- The Embryo Project for information on ESC research 516
- Concluding remarks about ethics of ESC research 516
- Ethical issues concerning umbilical cord blood 517
- Legal issues associated with stem cells 517
- Stem cell patents 517
- Stem cell patents in the United States 517
- Current status of Thomson patents at WARF 518
- Stem cell patents in the European Union 518
- Cell therapy tourism 519
9. Safety and Regulatory Aspects of Cell Therapy 521
- Introduction 521
- Safety issues of cell therapy 521
- Immune-mediated reactions to transpanted stem cells 521
- Human virus infections associated with stem cell transplantation 522
- Herpes simplex virus type 1 522
- Cytomegalovirus 522
- Opportunistic infections among hematopoietic stem cell transplant
recipients 522
- Cord colitis syndrome 522
- Carcinogenic potential of stem cells and its prevention 523
- FDA safety regulations for cell and tissue products 523
- FDA Guidance on license applications for umbilical cord blood products
524
- Regulation of cord blood banks in the US 524
- Regulatory issues for biotechnology-derived drugs 524
- Regulation of cell selection devices for PBSCs at point of care 525
- FDA rules for human cells and tissues 526
- FDA regulation of fetal cellular or tissue products 526
- FDA and clinical trials using hESCs 527
- Cell and gene therapy INDs placed on hold by the FDA 527
- Regulatory issues for genetically engineered cell transplants 528
- FDA guidelines for human tissue transplantation 528
- Xenotransplantation 528
- Clinical Protocol Review and Oversight 529
- Informed consent and patient education 529
- Xenotransplantation product sources 529
- FDA guidelines for xenografts 530
- Regulatory challenges for the clinical use of cell products 531
- Regulations relevant to cell therapy in the European Union 531
- Regulations about use of stem cells in the EU 533
- Guidelines for cell therapy in the UK 534
- NIH and stem cells 534
- hESC lines approved under the new NIH guidelines 534
- Clinical trials in cell therapy 535
Tables
- Table 1-1: Landmarks in the history of cell therapy 27
- Table 1-2: Examples of cells involved in various diseases 32
- Table 2-1: Types of human cells used in cell therapy 35
- Table 2-2: A selection of companies providing cell culture media 39
- Table 2-3: A sampling of companies supplying cell sorters 45
- Table 2-4: Companies involved in cell-based drug discovery 53
- Table 2-5: Methods of delivery of cells for therapeutic purposes 54
- Table 2-6: Therapeutic applications of encapsulated cells 58
- Table 2-7: Companies working on encapsulated cell technology 61
- Table 2-8: Molecular imaging methods for tracking cells in vivo 66
- Table 3-1: Companies involved in cord blood banking as a source of stem
cells 103
- Table 3-2: Companies providing iPSCs 110
- Table 3-3: Sources of adult human stem cells 115
- Table 3-4: Comparison of human stem cells according to derivation 124
- Table 3-5: Enhancing engraftment, mobilization and expansion of stem cells
144
- Table 3-6: Applications of stem cells 161
- Table 3-7: Advantages and limitations of methods for optimizing MSCs
172
- Table 3-8: Pharmaceutical manipulation of stem cells 178
- Table 3-9: Growth factors with positive effects on stem cells and
applications 180
- Table 3-10: Examples of drugs that induce granulocytopenia at stem cell
level 191
- Table 3-11: Academic institutes involved in stem cell research 198
- Table 3-12: Companies involved in stem cell technologies 200
- Table 4-1: Therapeutic applications of regulatory T cells (T-regs)
216
- Table 4-2: Various tissue/cell therapy approaches to the treatment of type
1 diabetes 223
- Table 4-3: Companies involved in cell therapy for insulin-dependent
diabetes 239
- Table 4-4: Major pulmonary disorders potentially treatable by stem cell
manipulation 256
- Table 4-5: Cell-based repair of knee cartilage damage 274
- Table 4-6: Intraoperative cell therapy 299
- Table 5-1: Classification of various types of cell therapy for
cardiovascular disorders 304
- Table 5-2: Clinical trials of cell therapy in cardiovascular disease
342
- Table 6-1: Cell therapy technologies used for cancer 349
- Table 6-2: Companies involved in developing cell-based therapies for
cancer 385
- Table 7-1: Experimental use of immortalized cells for CNS disorders
406
- Table 7-2: Combination of stem cells and HBO in models of neurological
disorders 412
- Table 7-3: Methods for delivering cell therapies in CNS disorders 413
- Table 7-4: Neurological disorders amenable to cell therapy 418
- Table 7-5: Types of cell used for investigative treatment of Parkinson's
disease 423
- Table 7-6: Status of cell therapies for Parkinson's disease 424
- Table 7-7: Role of cell therapy in management of stroke according to stage
448
- Table 7-8: Clinical trials of cell therapy for stroke: completed, ongoing
and pending 448
- Table 7-9: Clinical trials with cell-based therapies in neurological
disorders (excluding stroke) 488
- Table 8-1: Listed numbers of stem cell lines around the world 499
- Table 8-2: Stem cell policies around the world 500
- Table 8-3: European public attitudes about research involving human stem
cells 515
- Table 9-1: Possible adverse reactions and safety issues of cell therapy
521
Figures
- Figure 1-1: Interrelationships of cell therapy to other technologies
29
- Figure 1-2: Interrelationships of gene, cell and protein therapies
31
- Figure 3-1: A simplified biological scheme of embryonic stem Cells 74
- Figure 3-2: Steps of iPS cell production 107
- Figure 3-3: hESC-derived by somatic cell nuclear transfer 141
- Figure 3-4: Flow chart of development of stem cells with potential
bottlenecks 205
- Figure 5-1: Ex vivo vs in vivo approaches to regeneration of the heart
304
- Figure 5-2: hESC-derived cardiomyocytes from laboratory to bedside
317
- Figure 5-3: hESC-derived cardiomyocytes from laboratory to bedside
317
- Figure 5-4: Steps in growing a new heart in vitro for transplantation
339
- Figure 6-1: A scheme of generation and administration of tumor
antigen-pulsed dendritic cells 359
- Figure 6-2: Stem cell transplantation techniques 367
- Figure 7-1: Stem cells that can give rise to neurons 397
- Figure 7-2: Approaches to stem cell therapy in stroke 444
Part II
10. Markets and Future Prospects for Cell Therapy 6
- Introduction 6
- Methods for estimation of cell therapy markets 6
- Potential markets for cell therapy 7
- Markets according to technologies 7
- Stem cell transplants 7
- Supporting cell technologies 8
- Blood transfusion market 8
- Cord blood collection and storage 8
- Cell therapy and related technologies 8
- Cell therapy markets according to therapeutic area 8
- Bone and joint disorders 9
- Cancer 9
- Cardiovascular disorders 10
- Diabetes mellitus 10
- Liver disorders 11
- Neurological disorders 11
- Retinal degenerative diseases market 12
- Skin and wound care 12
- Urinary incontinence 12
- Reconstruction of teeth by stem cell implants 13
- Market size according to geographical areas 13
- Unmet market needs in cell therapy 14
- Drivers of growth of cell therapy markets 14
- Role of stem cells in regenerative medicine 14
- Role of cells in markets for artificial organs 15
- Increase of R&D expense on cell therapy 15
- Increased used of cell-based drug discovery 15
- Impact of emerging healthcare trends on cell therapy markets 15
- Markets for cell therapy tourism 16
- Involvement of pharmaceutical companies in cell therapy 16
- Future prospects of cell therapy 16
- Embryonic stem cell research around the world 16
- Consortia for ESC research in Europe 17
- EuroStemCell 17
- FunGenES 18
- ESTOOLS 18
- UK National Stem Cell Network 20
- Ethical concerns about commercialization of embryonic stem cells 20
- Education of the physicians 20
- Public education 20
- NIH support of stem cell research 21
- Funding of stem cell research from non-federal sources 21
- Prospects of venture capital support for stem cell companies 23
- Cell therapy in the developing countries 23
- Guidelines for stem cell therapies 24
- Business strategies 25
- Formation of networks 25
- Future market potential of adult vs embryonic stem cells 26
11. Companies Involved in Cell Therapy 28
- Introduction 28
- Profiles of selected companies 30
- Collaborations 343
12. Academic Institutions 352
- Introduction 352
- Stem cell center 352
- Profiles of institutions 353
- Collaborations 442
13. References 444
Tables
- Table 10-1: Market size according to cell therapy and related technologies
2012-2022 7
- Table 10-2: Market size according to therapeutic areas for cell therapy in
2012-2022 9
- Table 10-3: Cell therapy markets for cardiovascular disorders in 2012-2022
10
- Table 10-4: Values of cell therapies for neurological disorders in
2012-2022 11
- Table 10-5: Total cell therapy market in 2012-2022 according to
geographical areas 13
- Table 10-6: Cord blood market according to geographical areas 2012-2022
13
- Table 10-7: Stem cells transplant market according to geographical areas
2012-2022 13
- Table 11-1: Publicly traded cell therapy companies 28
- Table 11-2: Selected collaborations of cell therapy companies 343
- Table 12-1: Therapeutic uses of stem cells 360
- Table 12-2: Commercial collaborations of US academic institutes relevant
to stem cells 442
Figures
- Figure 10-1: Unmet needs in cell therapy 14
