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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 2011, and projected to 2021.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 278 of these are profiled in part II of the report along with tabulation of 268 alliances. Of these companies, 160 are involved in stem cells. Profiles of 69 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 52 Tables and 11 Figures. The bibliography contains 1,050 selected references, which are cited in the text.CELL THERAPY -1 TABLE OF CONTENTS 0. Executive Summary 231. Introduction to Cell Therapy 27Introduction 27Historical landmarks of cell therapy 27Interrelationship of cell therapy technologies 29Cells and organ transplantation 29Cells and protein/gene therapy 30Cell therapy and regenerative medicine 31Cells therapy and tissue engineering 31Therapy based on cells involved in disease 32Advantages of therapeutic use of cells 32Cell-based drug delivery 33Cells as vehicles for gene delivery 33Red blood cells as vehicles for drug delivery 33Advantages of cell-based drug delivery 34Limitations of cell-based drug delivery 342. Cell Therapy Technologies 35Introduction 35Cell types used for therapy 35Sources of cells 35Xenografts 36Cell lines 36Immortalized cells 36Blood component therapy 36Therapeutic apheresis 36Leukoreduction 37Platelet therapy 37Basic technologies for cell therapy 38Cell culture 38Automated cell culture devices 38Cell culture for adoptive cell therapy 39Observation of stem cell growth and viability 39Companies involved in cell culture 39Cell sorting 41Flow cytometry 41A dielectrophoretic system for cell separation 42Adult stem cell sorting by identification of surface markers 42ALDESORTER system for isolation of stem cells 42Dynabead technology for cell sorting 42Molecular beacons for specific detection and isolation of stem cells 43Multitarget magnetic activated cell sorter 43Nanocytometry 43Scepter™ cytometer 44Companies supplying cell sorters 44Cell analysis 45Cell analyzers 45In vivo cell imaging 45Measuring cell density 46Single-cell gene expression analysis 46Preservation of cells 47Innovations in cryopreservation 47Packaging of cells 48Selective expansion of T cells for immunotherapy 48Cloning and cell therapy 49Techniques for cell manipulation 49Cell-based drug discovery 50Advantages and limitations of cell-based assays for drug discovery 50Advantages and limitations of cell-based toxicity screening 50Quality control of cells for drug discovery 51Companies involved in cell-based drug discovery 51Drug delivery systems for cell therapy 53Intravenous delivery of stem cells 53Pharmacologically active microcarriers 53Devices for delivery of cell therapy 54Artificial cells 55Applications of artificial cells 55Cell encapsulation 55Diffusion capsule for cells 56Encapsulated cell biodelivery 56Therapeutic applications of encapsulated cells 56Nitric oxide delivery by encapsulated cells 58Implantation of microencapulated genetically modified cells 58Ferrofluid microcapsules for tracking with MRI 59Companies involved in encapsulated cell technology 59Electroporation 60Gene therapy 60Cell-mediated gene therapy 61Fibroblasts 61Chondrocyte 62Skeletal muscle cells 62Vascular smooth muscle cells 63Keratinocytes 63Hepatocytes 63Lymphocytes 63Mammalian artificial chromosomes 64In vivo tracking of cells 64Molecular imaging for tracking cells 64MRI technologies for tracking cells 65Superparamagnetic iron oxide nanoparticles as MRI contrast agents 66Visualization of gene expression in vivo by MRI 66Role of nanobiotechnology in development of cell therapy 66Cell transplantation for development of organs 67Cells transplantation and tolerance 67Strategies to improve tolerance of transplanted cells 68Encapsulation to prevent immune rejection 68Prevention of rejection of xenotransplants 68Expansion of allospecific regulatory T cells 68Removal and replacement of pathogenic cells of the body 69Therapeutic leukocytapheresis 693. Stem Cells 71Introduction 71Biology of stem cells 72Embryonic stem cells 72Growth and differentiation of ESCs 72Mechanisms of differentiation of ESCs 73Chemical regulation of stem cell differentiation 73In vitro differentiation of hESCs 73SIRT1 regulation during stem cell differentiation 73Regulation of stem cell self-renewal and differentiation 74hESCs for reprogramming human somatic nuclei 74Stem cells differentiation in the pituitary gland 74Influence of microenvironment on ESCs 75Role of genes in differentiation of ESCs 75Global transcription in pluripotent ESCs 75Role of p53 tumor suppressor gene in stem cell differentiation 76Role of Pax3 gene in stem cell differentiation 76Signaling pathways and ESC genes 76Epigenetics of hESCs 77Chromatin as gene regulator for ESC development 77Comparison of development of human and mouse ESCs 78Mechanism of regulation of stem cells for regeneration of body tissues 78Role of microenvironments in the regulation of stem cells 79Regulation and regeneration of intestinal stem cells 79Parthenogenesis and human stem cells 79Uniparental ESCs 80Bone marrow stem cells 81Hematopoietic stem cells 81Role of HSCs in the immune system 83Derivation of HSCs from ESCs 83Mesenchymal stem cells 83Multipotent adult progenitor cells 85Side population (SP) stem cells 85Differentiation of adult stem cells 86Growth and differentiation of HSCs 87Signaling pathways in the growth and differentiation of HSCs 87Mathematical modeling of differentiation of HSCs 87Role of prions in self renewal of HSCs 88Sources of stem cells 88Sources of of human embryonic stem cells 88Nuclear transfer to obtain hESCs 88Direct derivation of hESCs from embryos without nuclear transfer 89Alternative methods of obtaining hESCs 90Establishing hESC lines without destruction of embryo 90Altered nuclear transfer 91Small embryonic-like stem cells 91Advantages and disadvantages of ESCs for transplantation 92Use of ESC cultures as an alternative source of tissue for transplantation 92Spermatogonial stem cells 93Amniotic fluid as a source of stem cells 94Amniotic fluid stem cells for tissue repair and regeneration 94Generation of iPS cells from AF cells 94Placenta as source of stem cells 95Amnion-derived multipotent progenitor cells 95Placenta as a source of HSCs 96Umbilical cord as a source of MSCs 96Umbilical cord blood as source of neonatal stem cells 96Cryopreservation of UCB stem cells 97UCB as source of MSCs 98Applications of UCB 98Advantages of UCB 98Limitations of the use of UCB 99Licensing and patent disputes involving UCB 100Infections following UCB transplants 100Unanswered questions about UCB transplantation 101Companies involved in UCB banking 101UCB banking in the UK 102US national UCB banking system 103Future prospects of UCB as a source of stem cells 104Induced pluripotent stem cells derived from human somatic cells 104Characteristics of iPSCs 105DNA methylation patterns of iPS cells 105iPSCs derived from oocytes through SCNT 105iPSCs derived from skin 106iPSCs derived from blood 106Use of retroviral vectors for generation of iPSCs 107Use of non-integrating viral vectors for generation of iPSCs 107Generation of clinically relevant iPSCs 108Generation of RBCs from iPSCs 109iPSCs and disease modeling 109iPSCs for patient-specific regenerative medicine 110Concluding remarks about clinical potential of iPSCs 110Induced conditional self-renewing progenitor cells 110Sources of adult human stem cells 111Adipose tissue as a source of stem cells 111Intravenous infusion of adipose tissue derived MSCs 112iPSCs derived from adult human adipose stem cells 112Regulation of adipose stem cells differentiation 112Transforming adult adipose stem cells into other cells 113Multipotent stem-like cells derived from vascular endothelial cells 113Skin as a source of stem cells 113Controlling the maturation of embryonic skin stem cells 113Epidermal neural crest stem cells 114Follicle stem cells 114Mesenchymal stem cells in skin 115Regulation of stem cells in hair follicles 115Skin-derived precursor cells 115Stem cells in teeth 116Peripheral blood stem cells 116Spleen as a source of adult stem cells 117Search for master stem cells 117Vascular cell platform to self-renew adult HSC 117Adult stem cells vs embryonic stem cells 118Biological differences between adult and embryonic stem cells 118Neural crest stem cells from adult hair follicles 118Transdifferentiation potential of adult stem cells 119Limitations of adult stem cells 120Comparison of human stem cells according to derivation 120VENT cells 121Stem cell banking 121Stem cell technologies 122Analysis of stem cell growth and differentiation 122Tracking self-renewal and expansion of transplanted muscle stem cells 122Stem cell biomarkers 122Endoglin as a functional biomarker of HSCs 123STEMPRO? EZChek? for analysis of biomarkers of hESCs 123SSEA-4 as biomarker of MSCs 123p75NTR as a biomarker to isolate adipose tissue-derived stem cells 123Neural stem cell biomarker 124Protein expression profile as biomarker of stem cells 124Real-time PCR for quantification of protein biomarkers 124Study of stem cell pathways 125Study of stem cell genes 125Gene inactivation to study hESCs 125RNAi to study gene inactivation in hESCs 126Study of ESC development by inducible RNAi 126Targeting Induced Local Lesions in Genomes 127Homologous recombination of ESCs 127Immortalization of hESCs by telomerase 127Gene modification in genomes of hESCs and hiPSCs using zinc-finger nuclease 128miRNA and stem cells 128Role of miRNAs in gene regulation during stem cell differentiation 128Influence of miRNA on stem cell formation and maintenance 129Transcriptional regulators of ESCs control miRNA gene expression 129Stem cells and cloning 130Cell nuclear replacement and cloning 130Nuclear transfer and ESCs 130Cloning from differentiated cells 131Cloning mice from adult stem cells 132Creating interspecies stem cells 132Cloned cells for transplantation medicine 133Claims of cloning of hESCs 133Cytogenetics of embryonic stem cells 134Engraftment, mobilization and expansion of stem cells 135Adipogenesis induced by adipose tissue-derived stem cells 136Antisense approach for preservation and expansion of stem cells 136Biomatrials for ESC growth 137Chemoattraction of neuronal stem cells through GABA receptor 137Enhancement of HSC engraftment by calcium-sensing receptor 137Enhancement of stem cell differentiation by Homspera 138Ex vivo expansion of human HSCs in culture 138Ex vivo expansion of MSCs 139Ex vivo expansion of UCB cells for transplantation 139Expansion of HSCs in culture by inhibiting aldehyde dehydrogenase 139Expansion of adult stem cells by activation of Oct4 140Expansion of transduced HSCs in vivo 140Expansion of stem cells in vivo by Notch receptor ligands 140Mobilization of HSCs by growth factors 140Mobilization of stem cells by cytokines/chemokines 141Mobilization of adult human HSCs by use of inhibitors 142Mobilization of stem cells by HYC750 142Mobilization of stem cells by hyperbaric oxygen 143Mobilization by adenoviral vectors expressing angiogenic factors 143Selective mobilization of progenitor cells from bone marrow 143Selective Amplification 144Stem cell mobilization by acetylcholine receptor agonists 144Use of parathyroid hormone to increase HSC mobilzation 144Technologies for inducing differentiation of stem cells 145Generation of RBCs from hematopoietic stem cells 145Generation of multiple types of WBCs from hESCs and iPSCs 145Growth factor-induced differentiation of MAPCs 145Lineage selection to induce differentiation of hESCs 146Mechanical strain to induce MSC differentiation 146Neurotrophin-mediated survival and differentiation of hESCs 146Synthetic biology and stem cells 147Use of RNAi to expand the plasticity of autologous adult stem cells 147Use of carbohydrate molecules to induce differentiation of stem cells 148Limitations of the currently available stem cell lines in the US 148Stem cell separation 148Stem cell culture 149Culture of hMSCs 150Elimination of contaminating material in stem cell culture 150Long-term maintenance of MSC multipotency in culture 151Nanofiber scaffolds for stem cell culture 152Conversion of stem cells to functioning adipocytes 152Mass production of ESCs 152Promoting survival of dissociated hESCs 153Analysis and characterization of stem cells 153Havesting and identification of EPCs 153Labeling of stem cells 154Labeling, imaging and tracking of stem cells in vivo 154Perfluorocarbon nanoparticles to track therapeutic cells in vivo 154Project for imaging in stem cell therapy research 155Quantum dots for labeling and imaging of stem cells 155Superparamagnetic iron oxide nanoparticles for tracking MSCs 156Applications of stem cells 156Commercial development and applications of adult stem cells 157Retrodifferentiation of stem cells 157MultiStem 157Controlling the maintenance process of hematopoietic stem cells 157Self renewal and proliferation of HSCs 157Aging and rejuvenation of HSCs 158Peripheral blood stem cell transplantation 158Role of stem cells in regeneration 158Promotion of regeneration by Wnt/beta-catenin signaling 159Stem cells and human reproduction 159Expansion of spermatogonial stem cells 159Conversion of ESCs into spermatogonial stem cells 159Conversion of stem cells to oocytes 160ESCs for treatment of infertility in women 160Cloning human embryos from oocytes matured in the laboratory 161In utero stem cell transplantation 161Innovations in delivery of stem cells 162Polymeric capsules for stem cell delivery 163Immunological aspects of hESC transplantation 163Immunosuppression to prevent rejection of hESC transplants 163Histocompatibility of hESCs 163Strategies for promoting immune tolerance of hESCs 164Stem cells for organ vascularization 164Activation of EphB4 to enhance angiogenesis by EPCs 165Advantages and limitations of clinical applications of MSCs 165Biofusion by genetically engineering stem cells 166Stem cell gene therapy 166Combination of gene therapy with nuclear transfer 166Gene delivery to stem cells by artificial chromosome expression 167Genetic manipulation of ESCs 167Genetic engineering of human stem cells for enhancing angiogenesis 168HSCs for gene therapy 168Helper-dependent adenoviral vectors for gene transfer in ESCs 169Lentiviral vectors for in vivo gene transfer to stem cells 169Linker based sperm-mediated gene transfer technology 169Mesenchymal stem cells for gene therapy 169Microporation for transfection of MSCs 170Regulation of gene expression for SC-based gene therapy 170Stem cells and in utero gene therapy 170Therapeutic applications for hematopoietic stem cell gene transfer 171The future of hematopoietic stem cell gene therapy 171Stem cell pharmaceutics 171Cardiomyocytes derived from hESCs 171ESCs as source of models for drug discovery 172hESC-derived hepatocytes for drug discovery 173Pharmaceutical manipulation of stem cells 173Role of stem cells in therapeutic effects of drugs 175Stem cells for drug discovery 175Stem cells for drug delivery 176Stem cell activation for regeneration by using glucocortoids 176Toxicology and drug safety studies using ESCs versus other cells 177Future challenges for stem cell technologies 179Study of the molecular mechanism of cell differentiation 179MBD3-deficient ESC line 180In vivo study of human hemopoietic stem cells 180Stem cell biology and cancer 180Research into plasticity of stem cells from adults 181Stem cells and aging 181Activation of bone marrow stem cells into therapeutic cells 182Role of nitric oxide in stem cell mobilization and differentiation 183Stem cell genes 183Gene expression in hESCs 183The casanova gene in zebrafish 184Nanog gene 184Stem cell proteomics 185hESC phosphoproteome 186Proteomic studies of mesenchymal stem cells 186Proteomic profiling of neural stem cells 186Proteome Biology of Stem Cells Initiative 187Genomic alterations in cultured hESCs 187Hybrid embryos/cybrids for stem cell research 187Generation of patient-specific pluripotent stem cells 188Markers for characterizing hESC lines 189Switch of stem-cell function from activators to repressors 189Stem cell research at academic centers 190International Regulome Consortium 191Companies involved in stem cell technologies 191Concluding remarks about stem cells 196Challenges and future prospects of stem cell research 1974. Clinical Applications of Cell Therapy 199Introduction 199Cell therapy for hematological disorders 199Transplantation of autologous hematopoietic stem cells 199Hemophilias 199Ex vivo cell/gene therapy of hemophilia B 199Cell/gene therapy of hemophilia A 200Hematopoietic stem cell therapy for thrombocytopenia 201Stem cell transplant for sickle cell anemia 201Treatment of chronic acquired anemias 202Implantation of genetically engineered HSCs to deliver rhEpo 202Drugs acting on stem cells for treatment of anemia 202Stem cell therapy of hemoglobinopathies 203Stem cells for treatment of immunoglobulin-light chain amyloidosis 203Future prospects of cell therapy of hematological disorders 203Cell therapy for immunological disorders 204Role of dendritic cells in the immune system 204Modifying immune responses of DCs by vaccination with lipiodol-siRNA mixtures 204Potential of MSCs as therapy for immune-mediated diseases 205Stem cell therapy of chronic granulomatous disease 205Stem cell therapy of X-linked severe combined immunodeficiency 206Stem cell therapy of autoimmune disorders 206Treatment of rheumatoid arthritis with stem cells 206Treatment of Crohn's disease with stem cells 207Stem cell transplants for scleroderma 207Role of T Cells in immunological disorders 208Autologous T cells from adult stem cells 208Cell therapy for graft vs host disease 209MSCs for GVHD 210Cell therapy for viral infections 210T-cell therapy for CMV 210T-cell therapy for HIV infection 211T-cell immunity by Overlapping Peptide-pulsed Autologous Cells 211Anti-HIV ribozyme delivered in hematopoietic progenitor cells 212Dendritic-cell targeted DNA vaccine for HIV 212Cell therapy of lysosomal storage diseases 212Niemann-Pick disease 213Gaucher's disease 213Fabry's disease 214Cell therapy for diabetes mellitus 214Limitations of current treatment 215Limitations of insulin therapy for diabetes mellitus 215Limitations of pancreatic transplantation 215Islet cell transplantation 216Autologous pancreatic islet cell transplantation in chronic pancreatitis 216Clinical trials of pancreatic islet cell transplants for diabetes 216Drawbacks of islet cell therapy 217Use of an antioxidant peptide to improve islet cell transplantation 217Cdk-6 and cyclin D1 enhance human beta cell replication and function 218A device for delivery of therapeutic cells in diabetes 218Monitoring of islet cell transplants with MRI 218Concluding remarks about allogeneic islet transplantation for diabetes 219Encapsulation of insulin producing cells 219Encapsulated porcine pancreatic islet cells for pancreas 219Encapsulated insulinoma cells 220Magnetocapsule enables imaging/tracking of islet cell transplants 220Islet precursor cells 221Dedifferentiation of ? cells to promote regeneration 221Pharmacological approaches for ? cell regeneration 222Xenotransplantation of embryonic pancreatic tissue 222Non-pancreatic tissues for generation of insulin-producing cells 223Exploiting maternal microchimerism to treat diabetes in the child 223Bio-artificial substitutes for pancreas 223Role of stem cells in the treatment of diabetes 224Embryonic stem cells for diabetes 224HSC transplantation to supplement immunosuppressant therapy 225Human neural progenitor cells converted into insulin-producing cells 225Insulin-producing cells derived from UCB stem cells 226iPS cells for diabetes 226Isolation of islet progenitor cells 226Pancreatic progenitor cells Expansion in vitro 227Pancreatic stem cells 227Stem cell injection into portal vein of diabetic patients 227Dendritic cell-based therapy for type 1 diabetes 228Vaccine for diabetes 228Gene therapy in diabetes 228Viral vectors for gene therapy of diabetes 229Genetically engineered dendritic cells 229Genetically altered liver cells 229Genetically modified stem cells 230Companies developing cell therapy for diabetes 230Concluding remarks about cell and gene therapy of diabetes 231Cell therapy of gastrointestinal disorders 232Inflammatory bowel disease 232Cell therapy for liver disorders 233Types of cells and methods of delivery for hepatic disorders 233Bioartificial liver 234Limitations of bioartificial liver 235Stem cells for hepatic disorders 235Deriving hepatocytes from commercially available hMSCs 236Implantation of hepatic cells derived from hMSCs of adipose tissue 236MSC derived molecules for reversing hepatic failure 236Cell-based gene therapy for liver disorders 237Transplantation of genetically modified fibroblasts 237Transplantation of genetically modified hepatocytes 237Intraperitoneal hepatocyte transplantation 238Genetically modified hematopoietic stem cells 238Use of iPSCs derived from somatic cells for liver regeneration 238Clinical applications 238Future prospects of cell-based therapy of hepatic disorders 239Cell therapy of renal disorders 239Bioartificial kidney 240Cell-based repair for vascular access failure in renal disease 240Mesangial cell therapy for glomerular disease 240Stem cells for renal disease 241Role of stem cells in renal repair 241Bone marrow stem cells for renal disease 241MSC therapy for renal disease 242Cell therapy for pulmonary disorders 242Delivery of cell therapy for pumonary disorders 242Intratracheal injection of cells for pulmonary hypoplasia 242Role of stem cells in pulmonary disorders 243Lung stem cells 243Lung tissue regeneration from stem cells 243Role of stem cells in construction of the Cyberlung 244Respiratory epithelial cells derived from UCB stem cells 244Respiratory epithelial cells derived from hESCs 244Lung tissue engineering with adipose stromal cells 245Cell-based tissue-engineering of airway 245Pulmonary disorders that can be treatable with stem cells 245Acute lung injury and ARDS treated with MSCs 246Bronchopulmonary dysplasia treated with MSCs 247Chronic obstructive pulmonary disease treated with MSCs 247Cystic fibrosis treatment with genetically engineered MSCs 247Lung regeneration by integrin ?6?4-expressing alveolar epithelial cell 248Pulmonary arterial hypertension treatment with EPCs 248Cell therapy for disorders of bones and joints 249Repair of fractures and bone defects 249Adult stem cells for bone grafting 250Cell therapy for osteonecrosis 250Cell therapy for cervical vertebral interbody fusion 250ESCs for bone repair 251Intrauterine use of MSCs for osteogenesis imperfecta 251In vivo bone engineering as an alternative to cell transplantation 251MSCs for repair of bone defects 251MSCs for repair of bone fractures 254Osteocel 255Stem cells for repairing skull defects 255Stem cell-based bone tissue engineering 255Spinal fusion using stem cell-based bone grafts 256Osteoarthritis and other injuries to the joints 257Mosaicplasty 257Autologous cultured chondrocytes 257Autologous intervertebral disc chondrocyte transplantation 258Cartilage repair by genetically modified fibroblasts expressing TGF-? 259Generation of cartilage from stem cells 260Role of cell therapy in repair of knee cartilage injuries 261Role of cells in the repair of anterior cruciate ligament injury 263Autologous tenocyte implantation in rotator cuff injury repair 263Platelet injection for tennis elbow 264Cell therapy of rheumatoid arthritis 264Cell therapy for diseases of the eye 265Cell therapy for corneal repair 265Stem cell therapy for limbal stem cell deficiency 266Role of stem cells in fibrosis following eye injury 267Stem cell transplantation for radiation sickness 267MSCs for treatment of radiation damage to the bone 267MSCs for regeneration of ovaries following radiotherapy damage 268Cell therapy for regeneration 268Stem cells for regenerating organs 268Umbilical cord blood for regeneration 269Role of stem cells in regeneration of esophageal epithelium 269Cell therapy for regeneration of muscle wasting 269Wound healing: skin and soft tissue repair 270Cells to form skin substitutes for healing ulcers 271CellSpray for wound repair 271Cell therapy for burns 272Closure of incisions with laser guns and cells 273Follicular stem cells for skin and wound repair 273Reprogramming autologous stem cells for wound regeneration 274Role of amniotic fluid MSCs in repair of fetal wounds 274Genetically engineered keratinocytes for wound repair 274MSCs for wound healing 275Regeneration of aging skin by adipose-derived stem cells 275Repair of aging skin by injecting autologous fibroblasts 275Role of cells in tissue engineering and reconstructive surgery 275Stem cells for tissue repair 275Scaffolds for tissue engineering 276Improving vascularization of engineered tissues 276Enhancing vascularization by combining cell and gene therapy 277Choosing cells for tissue engineering 277ESCs vs adult SCs for tissue engineering 277Use of adult MSCs for tissue engineering 278Nanobiotechnology applied to cells for tissue engineering 279Stem cells for tissue engineering of various organs 279Engineering of healthy living teeth from stem cells 279Adipose tissue-derived stem cells for breast reconstruction 280Improving tissue engineering of bone by MSCs 281Intra-uterine repair of congenital defects using amniotic fluid MSCs 281Cell-based tissue engineering in genitourinary system 282Urinary incontinence 282Tissue engineering of urinary bladder 283Label retaining urothelial cells for bladder repair 283MSCs for bladder repair 284Tissue-engineering of urethra using autologous cells 284Repair of the pelvic floor with stem cells from the uterus 284Reconstruction of vagina from stem cells 285Facial skin regeneration by stem cells as an alternative to face transplant 285Reconstruction of cartilage for repair of craniofacial defects 285Cell therapy for rejuvenation 286Cell therapy for performance enhancement in sports 286Application of stem cells in veterinary medicine 286Use of stem cells to repair tendon injuries 286Stem cells for spinal cord injury in dogs 2875. Cell Therapy for Cardiovascular Disorders 289Introduction to cardiovascular disorders 289Limitations of current therapies for myocardial ischemic disease 289Types of cell therapy for cardiovascular disorders 289Cell-mediated immune modulation for chronic heart disease 290Human cardiovascular progenitor cells 291Inducing the proliferation of cardiomyocytes 291Pericardial origin of colony-forming units 292Role of the SDF-1-CXCR4 axis in stem cell therapies for myocardial ischemia 292Role of splenic myocytes in repair of the injured heart 292Reprogramming of fibroblasts into functional cardiomyocytes 293Small molecules to enhance myocardial repair by stem cells 293Cell therapy for atherosclerotic coronary artery disease 293MyoCell™ (Bioheart) 294Cardiac stem cells 294Cardiomyocytes derived from epicardium 295Methods of delivery of cells to the heart 296Cellular cardiomyoplasty 296IGF-1 delivery by nanofibers to improve cell therapy for MI 296Non-invasive delivery of cells to the heart by Morph®guide catheter 296Cell therapy for cardiac revascularization 297Transplantation of cardiac progenitor cells for revascularization of myocardium 297Stem cells to prevent restenosis after coronary angioplasty 297Role of cells in cardiac tissue repair 298Modulation of cardiac macrophages for repair of infarct 298Transplantation of myoblasts for myocardial infarction 298Patching myocardial infarction with fibroblast culture 299Cardiac repair with myoendothelial cells from skeletal muscle 299Myocardial tissue engineering 300Role of stem cells in repair of the heart 301Role of stem cells in cardiac regen
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