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 2007, and projected to 2017.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 246 of these are profiled in part II of the report along with tabulation of 235 alliances. Of these companies, 133 are involved in stem cells. Profiles of 60 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 44 Tables and 9 Figures. The bibliography contains 750 selected references, which are cited in the text.
Table of Contents
0. Executive Summary
1. Introduction to Cell Therapy
- Introduction
- Historical landmarks of cell therapy
- Interrelationship of cell therapy technologies
- Cells and organ transplantation
- Cells and protein/gene therapy
- Cell therapy and regenerative medicine
- Cells therapy and tissue engineering
- Therapy based on cells involved in disease
- Advantages of therapeutic use of cells
- Use of cells for improving drug delivery
2. Cell Therapy Technologies
- Introduction
- Cell types used for therapy
- Sources of cells
- Xenografts
- Cell lines
- Immortalized cells
- Blood component therapy
- Therapeutic apheresis
- Leukoreduction
- Platelet therapy
- Basic technologies for cell therapy
- Cell culture
- Observation of stem cell growth and viability
- Companies involved in cell culture
- Cell sorting
- Flow cytometry
- A dieltectrophoretic system for cell separation
- Companies supplying cell sorters
- Dynabead technology for cell sorting
- ALDESORTER system for isolation of stem cells
- Preservation of cells
- Packaging of cells
- Selective expansion of T cells for immunotherapy
- Cloning and cell therapy
- Techniques for cell manipulation
- Cell culture
- Cell-based drug discovery
- Cells as vehicles for drug delivery
- Drug delivery systems for cell therapy
- Devices for delivery of cell therapy
- Artificial cells
- Applications of artificial cells
- Cell encapsulation
- Diffusion capsule for cells
- Encapsulated cell biodelivery
- Therapeutic applications of encapsulated cells
- Nitric oxide delivery by encapsulated cells
- Implantation of microencapulated genetically modified cells
- Ferrofluid microcapsules for tracking with MRI
- Companies involved in encapsulated cell technology
- Electroporation
- Gene therapy
- Cell-mediated gene therapy
- Fibroblasts
- Chondrocyte
- Skeletal muscle cells
- Vascular smooth muscle cells
- Keratinocytes
- Hepatocytes
- Lymphocytes
- Mammalian artificial chromosomes
- Cell-mediated gene therapy
- In vivo tracking of cells
- Molecular imaging for tracking cells
- MRI technologies for tracking cells
- Superparamagnetic iron oxide nanoparticles as MRI contrast agents
- Visualization of gene expression in vivo by MRI
- Molecular imaging for tracking cells
- Role of nanobiotechnology in development of cell therapy
- Cell transplantation for development of organs
- Cells transplantation and tolerance
- Strategies to improve tolerance of transplanted cells
- Encapsulation to prevent immune rejection
- Prevention of rejection of xenotransplants
- Strategies to improve tolerance of transplanted cells
3. Stem Cells
- Introduction
- Biology of stem cells
- Embryonic stem cells
- Growth and differentiation of ESCs
- Regulation of stem cell self-renewal and differentiation
- Role of Pax3 in stem cell differentiation
- ESCs and signaling pathways
- Genetic signature of of stem cells
- Epigenetics of hESCs
- Chromatin as gene regulator for ESC development
- Mechanism of differentiation of ESCs
- Chemical regulation of stem cell differentiation
- Comparison of development of human and mouse ESCs
- In vitro differentiation of hESCs
- Global transcription in pluripotent ESCs
- Signaling pathways and transcription factors in ESCs
- Stem cells in the pituitary gland
- hESCs in stead of oocytes for reprogramming human somatic nuclei
- Mechanism of regulation of stem cells for regeneration of body tissues
- Role of microenvironments in the regulation of stem cells
- Regulation and regeneration of intestinal stem cells
- Parthenogenesis and human stem cells
- Uniparental ESCs
- Bone marrow stem cells
- Hematopoietic stem cells
- Role of HSCs in the immune system
- Derivation of HSCs from ESCs
- Mesenchymal stem sells
- Multipotent adult progenitor cells
- Side population (SP) stem cells
- Differentiation of adult stem cells
- Growth and differentiation of HSCs
- Signaling pathways in the growth and differentiation of HSCs
- Mathematical modeling of differentiation of HSCs
- Role of prions in self renewal of HSCs
- Hematopoietic stem cells
- Sources of stem cells
- Sources of of human embryonic stem cells
- Nuclear transfer to obtain hESCs
- Direct derivation of hESCs from embryos without nuclear transfer
- Alternative methods of obtaining hESCs
- Establishing hESC lines without destruction of embryo
- Altered nuclear transfer
- Small embryonic-like stem cells
- Advantages and disadvantages of ESCs for transplantation
- Use of ESC cultures as an alternative source of tissue for transplantation
- Spermatogonial stem cells
- Amniotic fluid as a source of stem cells
- Placenta as source of stem cells
- Amnion-derived multipotent progenitor cells
- Placenta as a source of HSCs
- Umbilical cord perivascular cells as a source of MSCs
- Umbilical cord blood as source of neonatal stem cells
- Cryopreservation of UCB stem cells
- Applications of UCB
- Advantages of UCB
- Limitations of the use of UCB
- Licensing and patent disputes involving UCB
- Infections following UCB transplants
- Unanswered questions about umbilical cord blood transplantation
- Companies involved in umbilical cord blood banking
- UCB banking in the UK
- US national UCB banking system
- Future prospects of UCB as a source of stem cells
- Sources of adult human stem cells
- Adipose tissue as a source of stem cells
- Skin as a source of stem cells
- Follicle stem cells
- Mesenchymal stem cells in skin
- Epidermal neural crest stem cells
- Regulation of stem cells in hair follicles
- Controlling the maturation of embryonic skin stem cells
- Stem cells in teeth
- Peripheral blood stem cells
- Spleen as a source of adult stem cells
- Search for master stem cells
- Adult stem cells vs embryonic stem cells
- Transdifferentiation potential of adult stem cells
- Neural crest stem cells from adult hair follicles
- Stem cells obtained from blood in adults
- Pluripotent stem cells derived from human somatic cells
- Use of retroviral vectors for generation of induced pluripotent cells
- Use of non-integrating viral vectors for generation of induced pluripotent cells
- VENT cells
- Stem cell technologies
- Analysis of stem cell growth and differentiation
- Tracking self-renewal and expansion of transplanted muscle stem cells
- Stem cell biomarkers
- Endoglin as a functional biomarker of HSCs
- STEMPRO® EZChek™ for analysis of biomarkers of hESCs
- SSEA-4 as biomarker of MSCs
- p75NTR as a biomarker to isolate adipose tissue-derived stem cells
- Neural stem cell biomarker
- Protein expression profile as biomarker of stem cells
- Gene inactivation to study hESCs
- RNAi to study gene inactivation in hESCs
- Study of ESC development by inducible RNAi
- Targeting Induced Local Lesions in Genomes
- Homologous recombination of ESCs
- Immortalization of hESCs by telomerase
- miRNA and stem cells
- Role of miRNAs in gene regulation during stem cell differentiation
- Influence of miRNA on stem cell formation and maintenance
- Transcriptional regulators of ESCs control miRNA gene expression
- Stem cells and cloning
- Cell nuclear replacement and cloning
- Nuclear transfer and ESCs
- Cloning from differentiated cells
- Cloning mice from adult stem cells
- Creating interspecies stem cells
- Cloned cells for transplantation medicine
- Claims of cloning of hESCs
- Cytogenetics of embryonic stem cells
- Engraftment, mobilization and expansion of stem cells
- Enhancement of HSC engraftment by calcium-sensing receptor
- Enhancement of stem cell differentiation by Homspera
- Stem cell mobilization by hyperbaric oxygen
- Mobilization of HSCs by growth factors
- Mobilization of stem cells by cytokines/chemokines
- Mobilization of adult human HSCs by use of inhibitors
- Mobilization of stem cells by HYC750
- Ex vivo expansion of human HSCs in culture
- Expansion of HSCs in culture by inhibiting aldehyde dehydrogenase
- Expansion of adult stem cells by activation of Oct4
- Selective Amplification
- Antisense approach for preservation and expansion of stem cells
- Mobilization by adenoviral vectors expressing angiogenic factors
- Stem cell mobilization by acetylcholine receptor agonists
- Expansion of transduced HSCs in vivo
- Use of parathyroid hormone to increase HSC mobilzation
- Expansion of stem cells in vivo by Notch receptor ligands
- Technologies for inducing differentiation of stem cells
- Use of lineage selection to induce differentiation of hESCs
- Growth factor-induced differentiation of MAPCs
- Neurotrophin-mediated survival and differentiation of hESCs
- Generation of RBCs from hematopoietic stem cells
- Use of RNAi to expand the plasticity of autologous adult stem cells
- Use of carbohydrate molecules to induce differentiation of stem cells
- Mechanical strain to induce MSC differentiation
- Limitations of the currently available stem cell lines in the US
- Contaminating material in stem cell culture and measures to eliminate it
- Stem cell separation
- Stem cell culture
- Conversion of stem cells to functioning adipocytes
- Mass production of ESCs
- Promoting survival of dissociated hESCs
- Analysis and characterization of stem cells
- Labeling of stem cells
- Quantum dots for labeling hMSCs
- Quantum dot imaging for ESCs
- Perfluorocarbon nanoparticles to track therapeutic cells in vivo
- Applications of stem cells
- Controlling the maintenance process of hematopoietic stem cells
- Peripheral blood stem cell transplantation
- Complications of PBSC transplantation in children
- Stem cell transplantation for radiation sickness
- Stem cells and human reproduction
- Expansion of spermatogonial stem cells
- Conversion of ESCs into spermatogonial stem cells
- Conversion of stem cells to oocytes
- ESCs for treatment of infertility in women
- Cloning human embryos from oocytes matured in the laboratory
- In utero stem cell transplantation
- Innovations in delivery of stem cells
- Immunological aspects of hESC transplantation
- Immunosuppression to prevent rejection of hESC transplants
- Histocompatibility of hESCs
- Strategies for promoting immune tolerance of hESCs
- Stem cells for organ vascularization
- Activation of EphB4 to enhance angiogenesis by EPCs
- Biofusion by genetically engineering stem cells
- Stem cell gene therapy
- Combination of gene therapy with nuclear transfer
- Gene delivery to stem cells by artificial chromosome expression
- Genetic manipulation of ESCs
- HSCs for gene therapy
- Helper-dependent adenoviral vectors for gene transfer in ESCs
- Lentiviral vectors for in vivo gene transfer to stem cells
- Linker based sperm-mediated gene transfer technology
- Mesenchymal stem cells for gene therapy
- Molecular vibration for gene transfer
- Regulation of gene expression for SC-based gene therapy
- Stem cells and in utero gene therapy
- Therapeutic applications for hematopoietic stem cell gene transfer
- The future of hematopoietic stem cell gene therapy
- Stem cell pharmaceutics
- Stem cells for drug discovery
- Advantages of using stem cells for drug discovery
- Role of stem cells in therapeutic effects of drugs
- Hepatocytes derived from hESCs
- Cardiomyocytes derived from hESCs
- ESCs as source of models for drug discovery
- Engineered stem cells for drug delivery to the brain
- Use of ESCs for toxicology and drug safety studies
- European projects for safety testing of drugs using ESCs
- Pharmaceutical manipulation of stem cells
- Adverse effects of drugs on stem cells
- Future challenges for stem cell technologies
- Study of the molecular mechanism of cell differentiation
- MBD3-deficient ESC line
- In vivo study of human hemopoietic stem cells
- Stem cell biology and cancer
- Research into plasticity of stem cells from adults
- Stem cells and aging
- Activation of bone marrow stem cells into therapeutic cells
- Role of nitric oxide in stem cell mobilization and differentiation
- Stem cell genes
- Gene expression in hESCs
- The casanova gene in zebrafish
- Nanog gene
- Stem cell proteomics
- Proteomic studies of mesenchymal stem cells
- Proteomic profiling of neural stem cells
- Proteome Biology of Stem Cells Initiative
- Genomic alterations in cultured hESCs
- Hybrid embryos/cybrids for stem cell research
- Generation of patient-specific pluripotent stem cells
- Markers for characterizing hESC lines
- Stem cell research at academic centers
- International Regulome Consortium
- Companies involved in stem cell technologies
- Concluding remarks about stem cells
- Challenges and future prospects of stem cell research
4. Clinical Applications of Cell Therapy
- Introduction
- Cell therapy for hematological disorders
- Transplantation of autologous hematopoietic stem cells
- Hemophilias
- Ex vivo cell/gene therapy of hemophilia B
- Ex vivo cell/gene therapy of hemophilia A
- Hematopoietic stem cell therapy for thrombocytopenia
- Stem cell transplant for sickle cell anemia
- Treatment of chronic acquired anemias
- Implantation of genetically engineered HSCs to deliver rhEpo
- Drugs acting on stem cells for treatment of anemia
- Stem cell therapy of hemoglobinopathies
- Stem cells for treatment of immunoglobulin-light chain amyloidosis
- Future prospects of cell therapy of hematological disorders
- Cell therapy for immunological disorders
- Modifying immune responses of DCs by vaccination with lipiodol-siRNA mixtures
- Stem cell therapy of chronic granulomatous disease
- Stem cell therapy of X-linked severe combined immunodeficiency
- Stem cell therapy of autoimmune disorders
- Treatment of Crohn' s disease with stem cells
- Treatment of rheumatoid arthritis with stem cells
- Stem cell transplants for scleroderma
- Role of T-Cells in immunological disorders
- Autologous T-cells from adult stem cells
- Cell therapy for graft vs host disease
- Cell therapy for viral infections
- T-cell therapy for CMV
- T-cell therapy for HIV infection
- T-cell immunity by Overlapping Peptide-pulsed Autologous Cells
- Dendritic-cell targeted DNA vaccine for HIV
- Cell therapy of lysosomal storage diseases
- Niemann-Pick disease
- Gaucher' s disease
- Fabry' s disease
- Cell therapy for diabetes mellitus
- Limitations of current treatment
- Limitations of insulin therapy for diabetes mellitus
- Limitations of pancreatic transplantation
- Islet cell transplantation
- Autologous pancreatic islet cell transplantation in chronic pancreatitis
- Clinical trials of pancreatic islet cell transplants for diabetes
- Drawbacks of islet cell therapy
- Use of an antioxidant peptide to improve islet cell transplantation
- A device for delivery of therapeutic cells in diabetes
- Monitoring of islet cell transplants with MRI
- Concluding remarks about allogeneic islet transplantation for diabetes
- Encapsulation of insulin producing cells
- Encapsulated porcine pancreatic islet cells for pancreas
- Encapsulated insulinoma cells
- Magnetocapsule enables imaging/tracking of islet cell transplants
- Islet precursor cells
- Dedifferentiation of β cells to promote regeneration
- Xenotransplantation of embryonic pancreatic tissue
- Non-pancreatic tissues for generation of insulin-producing cells
- Exploiting maternal microchimerism to treat diabetes in the child
- Bio-artificial substitutes for pancreas
- Role of stem cells in the treatment of diabetes
- Pancreatic stem cells
- Embryonic stem cells for diabetes
- Isolation of islet progenitor cells
- Expansion of pancreatic progenitor cells in vitro
- Human neural progenitor cells converted into insulin-producing cells
- Insulin-producing cells derived from UCB stem cells
- Stem cell injection into portal vein of diabetic patients
- HSC transplantation to supplement immunosuppressant therapy
- Dendritic cell-based therapy for type 1 diabetes
- Gene therapy in diabetes
- Viral vectors for gene therapy of diabetes
- Genetically engineered dendritic cells
- Genetically altered liver cells
- Genetically modified stem cells
- Companies developing cell therapy for diabetes
- Concluding remarks about cell and gene therapy of diabetes
- Limitations of current treatment
- Cell therapy for liver disorders
- Types of cells and methods of delivery for hepatic disorders
- Bioartificial liver
- Limitations of bioartificial liver
- Stem cells for hepatic disorders
- Deriving hepatocytes from commercially available hMSCs
- Implantation of hepatic cells derived from hMSCs of adipose tissue
- MSC derived molecules for reversing hepatic failure
- Cell-based gene therapy for liver disorders
- Transplantation of genetically modified fibroblasts
- Transplantation of genetically modified hepatocytes
- Intraperitoneal hepatocyte transplantation
- Genetically modified hematopoietic stem cells
- Clinical applications
- Future prospects of cell-based therapy of hepatic disorders
- Cell therapy of renal disorders
- Bioartificial kidney
- Bone marrow stem cells for renal disease
- Human stem cells to prevent end stage renal disease
- Role of stem cells in renal repair
- Cell-based repair for vascular access failure in renal disease
- Mesangial cell therapy
- Cell therapy for pulmonary disorders
- Delivery of cell therapy for pumonary disorders
- Intratracheal injection of cells for pulmonary hypoplasia
- Role of stem cells in pulmonary disorders
- Lung tissue regeneration from stem cells
- Role of stem cells in construction of the Cyberlung
- Respiratory epithelial cells derived from UCB stem cells
- Respiratory epithelial cells derived from hESCs
- Lung tissue engineering with adipose stromal cells
- Pulmonary disorders that are treatable by stem cell manipulation
- MSCs for acute lung injury and ARDS
- Genetically engineered MSCs for cystic fibrosis
- EPCs for treatment of pulmonary arterial hypertension
- Delivery of cell therapy for pumonary disorders
- Cell therapy for disorders of bones and joints
- Repair of fractures and bone defects
- Adult stem cells for bone grafting
- Stem cells for repairing skull defects
- Mesenchymal stem cells for repair of bones and joints
- Osteocel
- Cell therapy for osteonecrosis
- Intrauterine use of MSCs for osteogenesis imperfecta
- Stem cell-based bone tissue engineering
- In vivo bone engineering as an alternative to cell transplantation
- Osteoarthritis and other injuries to the joints
- Mosaicplasty
- Autologous cultured chondrocytes
- Autologous intervertebral disc chondrocyte transplantation
- Cartilage repair by genetically modified fibroblasts expressing TGF-β
- Generation of cartilage from stem cells
- Role of cell therapy in repair of knee cartilage injuries
- Role of cells in the repair of anterior cruciate ligament injury
- Autologous tenocyte implantation in rotator cuff injury repair
- Platelet injection for tennis elbow
- Cell therapy of rheumatoid arthritis
- Repair of fractures and bone defects
- Cell therapy for regeneration
- Stem cells and promotion of regeneration
- Umbilical cord blood for regeneration
- Promotion of regeneration by Wnt/beta-catenin signaling
- Role of stem cell fusion in regeneration
- Cell therapy for regeneration of muscle wasting
- MSCs for regeneration of ovaries following radiotherapy damage
- Wound healing: skin and soft tissue repair
- Cells to form skin substitutes for healing ulcers
- CellSpray for wound repair
- Role of follicular stem cells in skin and wound repair
- Cell therapy for burns
- Genetically engineered cells for wound repair
- Cell therapy for corneal repair
- Closure of incisions with laser guns and cells
- Repair of aging skin by injecting autologous fibroblasts
- Role of cells in tissue engineering and reconstructive surgery
- Stem cells for tissue repair
- Scaffolds for tissue engineering
- Improving vascularization of engineered tissues
- Enhancing vascularization by combining cell and gene therapy
- Choosing cells for tissue engineering
- ESCs vs adult SCs for tissue engineering
- Nanobiotechnology applied to cells for tissue engineering
- Stem cells for tissue engineering of various organs
- Engineering of healthy living teeth from stem cells
- Adipose tissue-derived stem cells for breast reconstruction
- Generation of complex organs from adult stem cells
- Strategies to improve stem cell transplantation for tissue engineering
- Use of adult MSCs for tissue engineering
- Improving tissue engineering of bone by MSCs
- Intra-uterine repair of congenital defects using amniotic fluid MSCs
- Cell-based tissue engineering in genitourinary system
- Urinary incontinence
- Tissue engineering of urinary bladder
- Label retaining urothelial cells for bladder repair
- Repair of the pelvic floor with stem cells from the uterus
- Reconstruction of vagina from stem cells
- Facial skin regeneration by stem cells as an alternative to face transplant
- Cell therapy for rejuvenation
- Cell therapy for performance enhancement in sports
- Application of stem cells in veterinary medicine
- Use of stem cells to repair tendon injuries
- Stem cells for spinal cord injury in dogs
5. Cell Therapy for Cardiovascular Disorders
- Introduction to cardiovascular disorders
- Limitations of current therapies for myocardial ischemic disease
- Cell-mediated immune modulation for chronic heart disease
- Human cardiovascular progenitor cells
- Inducing the proliferation of cardiomyocytes
- Small molecules to enhance myocardial repair by stem cells
- Cell therapy for atherosclerotic coronary artery disease
- Stem cells to prevent restenosis after coronary angioplasty
- Transplantation of myoblasts for myocardial infarction
- MyoCell™ (Bioheart)
- Transplantation of cardiac progenitor cells for revascularization of myocardium
- Methods of delivery of cells to the heart
- Cellular cardiomyoplasty
- IGF-1 delivery by nanofibers to improve cell therapy for MI
- Non-invasive delivery of cells to the heart by MorphRguide catheter
- Role of cells in cardiac tissue engineering
- Patching myocardial infarction with fibroblast culture
- Myocardial tissue engineering
- Role of stem cells in repair of the heart
- Cardiac stem cells
- Cardiomyocytes derived from epicardium
- Role of stem cells in cardiac regeneration following injury
- Studies to identify subsets of progenitor cells suitable for cardiac repair
- Technologies for preparation of stem cells for cardiovascular therapy
- Pravastatin for expansion of endogenous progenitor and stem cells
- Cytokine preconditioning of human fetal liver CD133+ SCs
- Expansion of adult cardiac stem cells for transplantation
- Role of ESCs in repair of the heart
- ESC transplantation for tumor-free repair of the heart
- Transplantation of stem cells for acute myocardial infarction
- Autologous bone marrow-derived stem cell therapeutics
- Autologous bone marrow-derived mesenchymal precursor stem cells
- Transplantation of cord blood stem cells
- Transplantation of hESCs
- Transplantation of HSCs
- Transplantation of autologous angiogenic cell precursors
- Transplantation of adipose-derived stem cells
- Intracoronary infusion of bone marrow-derived cells for AMI
- Intracoronary infusion of mobilized peripheral blood stem cells
- Transplantation of endothelial cells
- Transplantation of cardiomyocytes differentiated from hESCs
- Stem cell therapy for cardiac regeneration
- Regeneration of the chronic myocardial infarcts by HSC therapy
- Human mesenchymal stem cells for cardiac regeneration
- In vivo tracking of MSCs transplanted in the heart
- MSCs for hibernating myocardium
- Simultaneous transplantation of MSCs and skeletal myoblasts
- Transplantation of genetically modified cells
- Transplantation of genetically modified MSCs
- Transplantation of cells secreting vascular endothelial growth factor
- Transplantation of genetically modified bone marrow stem cells
- Cell transplantation for congestive heart failure
- Myoblasts for treatment of congestive heart failure
- Injection of adult stem cells for congestive heart failure
- AngioCell gene therapy for congestive heart failure
- Stem cell therapy for dilated cardiac myopathy
- Role of cell therapy in cardiac arrhythmias
- Atrioventricular conduction block
- Ventricular tachycardia
- Prevention of myoblast-induced arrhythmias by genetic engineering
- ESCs for correction of congenital heart defects
- Cardiac progenitors cells for treatment of heart disease
- Autologus stem cells for chronic myocardial ischemia
- Role of cells in cardiovascular tissue engineering
- Construction of blood vessels with cells
- Fetal cardiomyocytes seeding in tissue-engineered cardiac grafts
- UCB progenitor cells for engineering heart valves
- Stem cell therapy for peripheral vascular disease
- Clinical trials of cell therapy in cardiovascular disease
- Mechanism of the benefit of cell therapy for heart disease
- A critical evaluation of cell therapy for heart disease
- Publications of clinical trials of cell therapy for CVD
- Future directions for cell therapy of CVD
6. Cell Therapy for Cancer
- Introduction
- Cell therapy technologies for cancer
- Cellular immunotherapy for cancer
- Treatments for cancer by ex vivo mobilization of immune cells
- Granulocytes as anticancer agents
- Neutrophil granulocytes in antibody-based immunotherapy of cancer
- Cancer vaccines
- Autologous tumor cell vaccines
- Vaccines that simultaneously target different cancer antigens
- Gene modified cancer cells vaccines
- GVAX cancer vaccines
- Active immunotherapy based on antigen specific to the tumor
- The use of dendritic cells for cancer vaccination
- Basics of dendritic cell vaccines
- Preclinical and clinical studies with DC vaccines
- In vivo manipulation of dendritic cells
- Autologous dendritic cells loaded ex vivo with telomerase mRNA
- Dendritic/tumor cell fusion
- Genetically modified dendritic cells
- Limitations of DC vaccines for cancer
- Future developments to enhance clinical efficacy of DC vaccines
- Lymphocyte-based cancer therapies
- Adoptive immunotherapy
- Rescue of CD8+ T cells for use in tumor immunotherapy
- Expansion of antigen-specific cytotoxic T lymphocytes
- Genetically targeted T cells for treating B cell malignancies
- Tumor infiltrating lymphocytes
- Genetic engineering of tumor cells
- Hybrid cell vaccination
- Stem cell-based anticancer therapies
- Stem cell transplantation in cancer
- Peripheral blood stem cell transplantation
- Autologous stem cell transplantation
- Complications of stem cell transplants in cancer
- Long-term results of HSC transplantation
- Prediction of T-cell reconstitution after HSC transplantation.
- Mesenchymal stem cell transplantation in cancer
- Nonmyeloablative allogeneic hematopoietic stem cell transplantation
- Umbilical cord blood transplant for leukemia
- hESC-derived NK cells for treatment of cancer
- ESC vaccine for prevention of lung cancer
- Genetic modification of stem cells for cancer therapy
- Genetic modification of hematopoietic stem cells
- Use of hematopoietic stem cells to deliver suicide genes to tumors
- Delivery of anticancer agents by genetically engineered MSCs
- Mesenchymal progenitor cells for delivery of oncolytic adenoviruses
- Genetically modified NSCs for treatment of neuroblastoma
- Stem cell transplantation in cancer
- Innovations in cell-based therapy of cancer
- Use of immortalized cells
- Cancer therapy based on natural killer cells
- Mesothelin as a target for cancer immunotherapy
- Nanomagnets for targeted cell-based cancer gene therapy
- Implantation of genetically modified encapsulated cells for anticancer
therapy
- Antiangiogenesis therapy by implantation of microencapsulated cells
- Recombinant tumor cells secreting fusion protein
- NovaCaps™ for pancreatic cancer
- A device for filtering cancer and stem cells in the blood
- Cancer stem cells
- Role of integrative nuclear signaling in stem cell development
- Breast cancer stem cells
- Role of intestinal stem cells in intestinal polyposis
- Role of endothelial progenitor cells in tumor angiogenesis
- Role of cancer stem cells in metastases
- Therapeutic implications of cancer stem cells
- Targeting cancer stem cells in leukemia
- Targeting stem cells in ovarian cancer
- Cell-based therapies for malignant brain tumors
- Role of cancer stem cells in resistance to radiotherapy
- Targeting stem cells in brain tumors
- Neural stem cells for drug/gene delivery to brain tumors
- Mesenchymal stem cells for the treatment of gliomas
- Bone morphogenetic protein for inhibition of glioblastoma multiforme
- Dendritic cell therapy for brain tumors
- Encapsulated cells for brain tumors
- Companies involved in cell-based cancer therapy
- American Association for Cancer Research and ESCs
- Future of cell-based immunotherapy for cancer
7. Cell Therapy for Neurological Disorders
- Introduction
- Regeneration of the nervous system by endogenous stem cells
- Molecular mechanism of neurogenesis
- Generation of neurons from astroglia
- Types of cells used for treatment of neurological disorders
- Activated T lymphocytes
- Differentiation of placenta-derived multipotent cells into neurons
- Neural stem cells
- Regulation of neural stem cells in the brain
- Study of neural differentiation of hESCs by NeuroStem Chip
- Embryonic stem cell-derived neurogenesis
- Neural progenitor cells
- Distinction between NSCs and intermediate neural progenitors
- Development of human CNS stem cells
- Neural stem cells in the subventricular zone of the brain
- Mechanism of migration of neural stem cells to sites of CNS injury
- Transformation of neural stem cells into other cell types
- Monitoring of implanted NSCs labeled with nanoparticles
- Oligodendrocyte progenitor cells
- Proteomics of neural stem cells
- Use of epidermal neural crest stem cells for neurological disorders
- Neural stem cells as therapeutic delivery vehicles
- Olfactory epithelium stem cells for transplantation in the CNS
- Development of CNS cells from extraneural stem cells
- Hair-follicle stem cells for neural repair
- Stem cells from human umbilical cord blood for CNS disorders
- Immortalized cells for CNS disorders
- Fetal tissue transplants
- Choroid plexus cells
- Laboratory mice with human brain cells
- Expansion of adult human neural progenitors
- Neurospheres
- Ideal cells for transplantation into the nervous system
- Cell therapy techniques for neurological applications
- Stem cells preparations for CNS disorders
- Neuronal differentiation of stem cells
- hESCs for CNS repair
- Enhancement of growth of stem cells in the brain by drugs
- Carbon nanotubes to aid stem cell therapy of neurological disorders
- Use of neural stem cells to construct the blood brain barrier
- Tracking of stem cells in the CNS by nanoparticles and MRI
- Methods of delivery of cells to the CNS
- Encapsulated cells
- CNS neotissue implant
- CNS delivery of cells by catheters
- Intravascular administration
- Cells used for gene therapy of neurological disorders
- Fibroblasts
- Stem cells
- Neuronal cells
- Immortalized neural progenitor cells
- Astrocytes
- Cerebral endothelial cells
- Human retinal pigmented epithelial cells
- Neurological disorders amenable to cell therapy
- Neuroprotection by cell therapy
- Cells secreting neuroprotective substances
- Stem cells for neuroprotection
- Neuroprotection by intravenous administration of HSCs
- Human UCB-derived stem cells for the aging brain
- Neurodegenerative disorders
- Role of stem cells in neurodegenerative disorders
- MSCs for therapy of neurodegenerative disorders
- Role of NSCs in disorders associated with aging brain
- NSCs for improving memory
- Parkinson' s disease
- Origin and fate of dopamine neurons
- Human dopaminergic neurons for PD
- Graft survival-enhancing drugs
- Xenografting porcine fetal neurons
- Encapsulated cells for PD
- Stem cells for PD
- Stem cells for production of glial derived neurotrophic factor
- Potential of regeneration of endogenous stem cells in PD
- Human retinal pigment epithelium cells for PD
- Coaxing hESCs to produce dopamine
- Tumorigenic potential of transplantated dopaminergic hESCs
- Delivery of cells for PD
- MSCs for multiple system atrophy
- Cell therapy for Huntington' s disease
- Fetal striatal cell transplantation
- Transplantation of encapsulated porcine choroids plexus cells
- Cell therapy for Alzheimer' s disease
- Neural stem cell implantation for Alzheimer' s disease
- Implantation of genetically engineered cells producing NGF
- Cell therapy for amyotrophic lateral sclerosis
- Cell nuclear replacement technique for study of ALS
- Use of stem cells for ALS
- Transplantation of glial restricted precursors in ALS
- Stem cell-based drug discovery for ALS
- Cell therapy for lysosomal storage disorders
- Cell therapy for Batten disease
- Genetically modified HSCs for metachromatic leukodystrophy
- Cell therapy for demyelinating disorders
- Hematopoietic stem cell transplantation for multiple sclerosis
- Embryonic stem cells for remyelination
- Neural precursor cells for neuroprotection in multiple sclerosis
- Stem cell transplantation for chronic inflammatory demyelinating polyneuropathy
- Cell therapy of stroke
- Transplantation of encapsulated porcine choroids plexus
- Transplantation of fetal porcine cells
- Adult stem cell therapy in stroke
- Implantation of genetically programmed ESCs
- Intravenous infusion of marrow stromal cells
- Intravenous infusion of umbilical cord blood stem cells
- Intracerebral administration of human adipose tissue stromal cells
- Intracerebral administration of multipotent adult progenitor cells
- Neural stem cell therapy for stroke
- Future of cell therapy for stroke
- Cell therapy of traumatic brain injury
- Clinical trials of autologous HSC therapy for TBI
- Limitations of stem cell therapy for acute TBI
- Cell therapy for spinal cord injury
- Fetal neural grafts for SCI
- Olfactory-ensheathing cells for SCI
- Oligodendrocyte precursor cells for treatment of SCI
- Schwann cell transplants for SCI
- Transplantation of glial cells for SCI
- Stem cells for SCI
- Bone marrow stem cells for SCI
- Embryonic stem cells for SCI
- Transplantation of MSCs for SCI
- Transplantation of NSCs for SCI
- Spinal stem cells for treatment of ischemic injury of spinal cord
- Combined approaches for regeneration in SCI
- Combined cell/gene therapy for SCI
- Delivery of cells in SCI
- Intrathecal injection of cells labeled with magnetic nanoparticles
- Intravenous injection of stem cells for spinal cord repair
- Clinical applications of stem cells for SCI
- Autologous bone marrow cell transplantation for SCI
- Cell therapy of syringomyelia
- Cell transplants for peripheral nerve injuries
- Umbilical cord blood stem cells for neurogenetic disorders
- UCB stem cells for Krabbe' s disease
- UCB stem cells for Hurler' s syndrome
- UCB stem cells for Sanfilippo syndrome type B
- Combination of cell and gene therapy for Krabbe' s disease
- Cell therapy of epilepsy
- Cell therapy of posttraumatic epilepsy
- Cell therapy for temporal lobe epilepsy
- Cell therapy for pharmacoresistant epilepsies
- Cell therapy for developmental neurological disorders
- Cell therapy for cerebral palsy
- Cell therapy for muscular dystrophy
- Cell transplant for Duchenne muscular dystrophy
- Myoblast-based gene transfer
- Transplantation of myoblasts lacking the MyoD gene
- HSCs for DMD
- Improvement of DMD therapy by using muscle-derived stem cells
- Combination of cell and pharmacotherapy for DMD
- Cell therapy for Autism
- Management of chronic intractable pain by cell therapy
- Implantation of chromaffin cells
- Role of stem cells in management of pain
- Implantation of astrocytes secreting enkephalin
- Cells for delivery of antinociceptive molecules
- Implantation of genetically engineered cells
- Cell therapy for low back pain
- Cell therapy for retinal degenerative disorders
- Genetically engineered retinal pigmented epithelial cell lines
- Delivery of CNTF by encapsulated cell intraocular implants
- Stem cell transplantation in the retina
- Human retinal stem cells
- Isolation of RPE cells from hESCs using transcriptomics
- ESCs for retinal degenerative disorders
- Neuroprotective effect of neural progenitor cell transplantation
- Combining cell and gene therapies for retinal disorders
- Stem cell therapy for hearing loss
- Cells secreting neuroprotective substances
- Clinical trials of cell therapy in neurological disorders
- Future prospects for cell therapy of CNS disorders
8. Ethical, Regulatory, and Safety Aspects of Cell Therapy
- Introduction
- Safety issues of cell therapy
- Immune-mediated reactions to transpanted stem cells
- Human virus infections associated with stem cell transplantation
- Herpes simplex virus type 1
- Cytomegalovirus
- Opportunistic infections among hematopoietic stem cell transplant recipients
- Carcinogenic potential of stem cells and its prevention
- FDA safety regulations for cell and tissue products
- FDA Guidance on license applications for umbilical cord blood products
- Political and ethical aspects of hESC research in the US
- Ethical issues concerning fetal tissues
- Morality and hESC research
- Opponents of hESC research in the US
- Ban on cloning and impact on hESC research
- Political aspects of human hESC research in the US
- Use of hESCs in NIH-supported research
- Public opinion in the US about hESC research
- Scientists' view of stem cell research in the US
- New developments in stem cell research in the US
- Human stem cell cloning in the US
- Stem cell guidelines of various US institutions
- Ethics of transplanting human NSCs into the brains of nonhuman primates
- Ethical issues concerning fetal tissues
- Stem cell lines available worldwide
- Stem cell policies around the world
- Countries with no defined policies on hESC research
- Australia
- Canada
- China
- Denmark
- France
- Germany
- India
- Ireland
- Israel
- Italy
- Japan
- The Netherlands
- Saudi Arabia
- Singapore
- South Africa
- South Korea
- Spain
- Sweden
- Switzerland
- United Kingdom
- ESC bank
- European Union
- EU guidelines for stem cell research
- EMBO' s recommendations for stem cell research
- United Nations, cloning and nuclear transfer
- The Embryo Project for information on ESC research
- Concluding remarks about ethics of ESC research
- Ethical issues concerning umbilical cord blood
- Regulatory issues
- Regulation of cord blood banks in the US
- Regulatory issues for biotechnology-derived drugs
- Regulation of cell selection devices for production of PBSCs at point of care
- FDA rules for human cells and tissues
- FDA regulation of fetal cellular or tissue products
- FDA and clinical trials using hESCs
- NIH regulation of fetal cellular or tissue products
- Regulatory issues for genetically engineered cell transplants
- FDA guidelines for human tissue transplantation
- Xenotransplantation
- Clinical Protocol Review and Oversight
- Informed consent and patient education
- Xenotransplantation product sources
- FDA guidelines for xenografts
- Regulations relevant to cell therapy in the European Union
- Guidelines for cell therapy in the UK
- Regulations about use of stem cells
- Stem cell patents
- Stem cell patents in the United States
- Current status of Thomson patents at WARF
- Stem cell patents in the European Union
- Stem cell patents in the United States
9. Markets and Future Prospects for Cell Therapy
- Introduction
- Methods for estimation of cell therapy markets
- Potential markets for cell therapy
- Markets according to technologies
- Stem cell transplant
- Blood transfusion market
- Cord blood collection and storage
- Cell therapy and related technologies
- Cell therapy markets according to therapeutic area
- Bone and joint disorders
- Cancer
- Cardiovascular disorders
- Diabetes mellitus
- Liver disorders
- Neurological disorders
- Retinal degenerative diseases market
- Skin and wound care
- Urinary incontinence
- Reconstruction of teeth by stem cell implants
- Markets according to technologies
- Market size according to geographical areas
- Unmet market needs in cell therapy
- Future prospects of cell therapy
- Role of stem cells in regenerative medicine
- Role of cells in markets for artificial organs
- Clinical trials in cell therapy
- Embryonic stem cell research around the world
- Consortia for ESC research in Europe
- EuroStemCell
- FunGenES
- ESTOOLS
- UK National Stem Cell Network
- Ethical concerns about commercialization of embryonic stem cells
- Education of the physicians
- Public education
- NIH support of stem cell research
- Funding of stem cell research from non-federal sources
- Prospects of venture capital support for stem cell companies
- Cell therapy in the developing countries
- Guidelines for stem cell therapies
- Business strategies
- Formation of networks
- Future market potential of adult vs embryonic stem cells
10. References
Tables
- Table 1 - 1: Landmarks in the history of cell therapy
- Table 1 - 2: Examples of cells involved in various diseases
- Table 2 - 1: Types of human cells used in cell therapy
- Table 2 - 2: A selection of companies providing cell culture media
- Table 2 - 3: A sampling of companies supplying cell sorters
- Table 2 - 4: Companies involved in cell-based drug discovery
- Table 2 - 5: Methods of delivery of cells for therapeutic purposes
- Table 2 - 6: Therapeutic applications of encapsulated cells
- Table 2 - 7: Companies working on encapsulated cell technology
- Table 2 - 8: Methods for tracking cells in vivo
- Table 3 - 1: Companies involved in cord blood banking as a source of stem cells
- Table 3 - 2: Sources of adult human stem cells
- Table 3 - 3: Enhancing engraftment, mobilization and expansion of stem cells
- Table 3 - 4: Applications of stem cells
- Table 3 - 5: Growth factors with positive effects on stem cells and applications
- Table 3 - 6: Examples of drugs that induce granulocytopenia at stem cell level
- Table 3 - 7: Academic institutes involved in stem cell research
- Table 3 - 8: Companies involved in stem cell technologies
- Table 4 - 1: Therapeutic applications of regulatory T cells (T-regs)
- Table 4 - 2: Various tissue/cell therapy approaches to the treatment of type 1 diabetes
- Table 4 - 3: Companies involved in cell therapy for insulin-dependent diabetes
- Table 4 - 4: Major pulmonary disorders potentially treatable by stem cell manipulation
- Table 4 - 5: Cell-based repair of knee cartilage damage
- Table 5 - 1: Clinical trials of cell therapy in cardiovascular disease
- Table 6 - 1: Cell therapy technologies used for cancer
- Table 6 - 2: Companies involved in developing cell-based therapies for cancer
- Table 7 - 1: Experimental use of immortalized cells for CNS disorders
- Table 7 - 2: Methods for delivering cell therapies in CNS disorders
- Table 7 - 3: Neurological disorders amenable to cell therapy
- Table 7 - 4: Types of cell used for investigative treatment of Parkinson' s disease
- Table 7 - 5: Cell therapies in development for Parkinson' s disease
- Table 7 - 6: Clinical trials with cell-based therapies in neurological disorders
- Table 8 - 1: Possible adverse reactions and safety issues of cell therapy
- Table 8 - 2: Numbers of stem cell lines around the world
- Table 8 - 3: Stem cell policies around the world
- Table 9 - 1: Market size according to cell therapy and related technologies 2007-2017
- Table 9 - 2: Market size according to therapeutic areas for cell therapy 2007-2017
- Table 9 - 3: Cell therapy markets for cardiovascular disorders 2007-2017
- Table 9 - 4: Values of cell therapies for neurological disorders 2007-2017
- Table 9 - 5: Total cell therapy market according to geographical areas 2007-2017
- Table 9 - 6: Cord blood market according to geographical areas 2007-2017
- Table 9 - 7: Stem cells transplant market according to geographical areas 2007-2017
Figures
- Figure 1 - 1: Interrelationships of cell therapy to other technologies
- Figure 1 - 2: Interrelationships of gene, cell and protein therapies
- Figure 3 - 1: A simplified biological scheme of embryonic stem Cells
- Figure 3 - 2: Flow chart of development of stem cells with potential bottlenecks
- Figure 6 - 1: A scheme of generation and administration of tumor antigen-pulsed dendritic cells
- Figure 6 - 2: Stem cell transplantation techniques
- Figure 7 - 1: Stem cells that can give rise to neurons
- Figure 7 - 2: Approaches to stem cell therapy in stroke
- Figure 9 - 1: Unmet needs in cell therapy
