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Cell Therapy - Technologies, Markets and Companies
Jain PharmaBiotech, Nov 2009, Pages: 935
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 dielectrophoretic system for cell separation
Molecular beacons for specific detection and isolation of stem cells
Multitarget magnetic activated cell sorter
Nanocytometry
Companies supplying cell sorters
Dynabead technology for cell sorting
ALDESORTER system for isolation of stem cells
Adult stem cell sorting by identification of surface markers
Cell analysis
Preservation of cells
Innovations in cryopreservation
Packaging of cells
Selective expansion of T cells for immunotherapy
Cloning and cell therapy
Techniques for cell manipulation
Cell-based drug discovery
Cells as vehicles for drug delivery
Drug delivery systems for cell therapy
Intravenous delivery of stem cells
Pharmacologically active microcarriers
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
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
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
Expansion of allospecific regulatory T cells
Removal and replacement of pathogenic cells of the body
Therapeutic leukocytapheresis
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 cells
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
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 as a source of MSCs
Umbilical cord blood as source of neonatal stem cells
Cryopreservation of UCB stem cells
UCB as source of MSCs
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 UCB transplantation
Companies involved in UCB banking
UCB banking in the UK
US national UCB banking system
Future prospects of UCB as a source of stem cells
Induced pluripotent stem cells derived from human somatic cells
Characteristics of iPSCs
Use of retroviral vectors for generation of iPSCs
Use of non-integrating viral vectors for generation of iPSCs
iPSCs derived from blood
iPSCs derived from skin
Clinical relevance of iPSCs
Sources of adult human stem cells
Adipose tissue as a source of stem cells
Transforming adult adipose stem cells into other cells
iPSCs derived from adult human adipose 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
VENT cells
Stem cell banking
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
STEMPROÒ EZChekä 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
Real-time PCR for quantification of protein biomarkers
Study of stem cell genes
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
Gene modification in genomes of hESCs and hiPSCs using zinc-finger nuclease
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
Adipogenesis induced by adipose tissue-derived stem cells
Antisense approach for preservation and expansion of stem cells
Enhancement of HSC engraftment by calcium-sensing receptor
Enhancement of stem cell differentiation by Homspera
Ex vivo expansion of human HSCs in culture
Ex vivo expansion of MSCs
Expansion of HSCs in culture by inhibiting aldehyde dehydrogenase
Expansion of adult stem cells by activation of Oct4
Expansion of transduced HSCs in vivo
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
Mobilization of stem cells by hyperbaric oxygen
Mobilization by adenoviral vectors expressing angiogenic factors
Selective mobilization of progenitor cells from bone marrow
Selective Amplification
Stem cell mobilization by acetylcholine receptor agonists
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
Generation of multiple types of WBCs from hESCs and iPSCs
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
Havesting and identification of EPCs
Labeling of stem cells
Quantum dots for labeling hMSCs
Imaging and tracking of stem cells in vivo
Quantum dot imaging for ESCs
Perfluorocarbon nanoparticles to track therapeutic cells in vivo
Project for imaging in stem cell therapy research
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
Genetic engineering of human stem cells for enhancing angiogenesis
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
hESC phosphoproteome
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
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
Role of dendritic cells in the immune system
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
Anti-HIV ribozyme delivered in hematopoietic progenitor 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
Cdk-6 and cyclin D1 enhance human beta cell replication and function
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 b 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
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
Cell-based tissue-engineering of airway
Pulmonary disorders that are treatable by stem cells
Acute lung injury and ARDS treated with MSCs
Cystic fibrosis treatment with genetically engineered MSCs
Pulmonary arterial hypertension treatment with EPCs
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-ß
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
Cell therapy for regeneration
Stem cells for regeneration
Stem cells for regenerating organs
Umbilical cord blood for regeneration
Promotion of regeneration by Wnt/beta-catenin signaling
Role of stem cells in regeneration of esophageal epithelium
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
Use of adult MSCs 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
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
Tyes of cell therapy for cardiovascular disorders
Cell-mediated immune modulation for chronic heart disease
Role of splenic myocytes in repair of the injured heart
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
MyoCell™ (Bioheart)
Cardiac stem cells
Cardiomyocytes derived from epicardium
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 Morph®guide catheter
Cell therapy for cardiac revascularization
Transplantation of cardiac progenitor cells for revascularization of myocardium
Stem cells to prevent restenosis after coronary angioplasty
Role of cells in cardiac tissue repair
Transplantation of myoblasts for myocardial infarction
Patching myocardial infarction with fibroblast culture
Cardiac repair with myoendothelial cells from skeletal muscle
Myocardial tissue engineering
Role of stem cells in repair of the heart
Role of stem cells in cardiac regeneration following injury
Cardiomyocytes derived from ESCs
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
Genetically engineered cells as biological pacemakers
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
Targeted delivery of endothelial progenitor cells labeled with nanoparticles
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
Prospects of adult stem cell therapy for repair of heart
Regeneration of cardiomyocytes without use of cardiac stem cells
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
HSC transplantation followed by GM-CSF-secreting cell vaccines
Role of mesenchymal stem cells 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
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
NovaCapsÒ, 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
Cancer stem cell markers
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
Targeting cancer stem cells to screen anticancer drugs
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
In vivo cell replacement therapy by locally induced neural progenitor cells
Types of cells used for treatment of neurological disorders
Activated T lymphocytes
Differentiation of placenta-derived multipotent cells into neurons
Mesenchymal stem cells induced to secrete neurotrophic factors
Neural stem cells
Development of human CNS stem cells
Distinction between NSCs and intermediate neural progenitors
Embryonic stem cell-derived neurogenesis
Mechanism of migration of neural stem cells to sites of CNS injury
Monitoring of implanted NSCs labeled with nanoparticles
Neural progenitor cells
Neural stem cells as therapeutic delivery vehicles
Neural stem cells in the subventricular zone of the brain
Oligodendrocyte progenitor cells
Proteomics of neural stem cells
Regulation of neural stem cells in the brain
Study of neural differentiation of hESCs by NeuroStem Chip
Transformation of neural stem cells into other cell types
Use of epidermal neural crest stem cells for neurological disorders
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
Dental pulp cells for neuroprotection
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
Intrathecal delivery of stem cells
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 cells for chronic inflammatory demyelinating polyneuropathy
Fusokine method of personalized cell therapy of multiple sclerosis
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 UCB 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
Cell/gene therapy for TBI
Clinical trials of autologous HSC therapy for TBI
Limitations of stem cell therapy for acute TBI
Improving the microenvironments of transplanted cells in 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
Transdifferentiation of BM stem cells into cholinergic neurons 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
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
Myoblast injection for treatment of other muscular dystrophies
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
Isolation of RPE cells from hESCs using transcriptomics
ESCs for retinal degenerative disorders
Neuroprotective effect of neural progenitor cell transplantation
Human retinal stem cells
Combining cell and gene therapies for retinal disorders
Stem cell therapy for hearing loss
Cell thery for peripheral nerve lesions
Cell transplants for peripheral nerve injuries
Treatment of diabetic neuropathy with endothelial progenitor cells
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
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
Cell therapy tourism
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
Cell and gene therapy INDs placed on hold by the FDA
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
Regulations about use of stem cells
EMEA regulation of cell/gene therapy
Guidelines for cell therapy in the UK
Clinical trials in cell therapy
Stem cell patents
Stem cell patents in the United States
Current status of Thomson patents at WARF
Stem cell patents in the European Union
9. 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: Molecular imaging 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: Classification of various types of cell therapy for cardiovascular disorders
Table 5-2: 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: Status of cell therapies 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: Listed numbers of stem cell lines around the world as of end of 2008
Table 8-3: Stem cell policies around the world
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: Steps of iPS cell production
Figure 3-3: Flow chart of development of stem cells with potential bottlenecks
Figure 5-1: hESC-derived cardiomyocytes from laboratory to bedside
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
10. 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
hESC markets
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
Market size according to geographical areas
Unmet market needs in cell therapy
Drivers of growth of cell therapy markets
Role of stem cells in regenerative medicine
Role of cells in markets for artificial organs
Increase of R&D expense on cell therapy
Increased used of cell-based drug discovery
Impact of emerging healthcare trends on cell therapy markets
Future prospects of 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
11. Companies Involved in Cell Therapy
Introduction
Profiles of selected companies
Collaborations
12. Academic Institutions
Introduction
Stem cell center
Profiles of institutions
Collaborations
Tables
Table 10-1: Market size according to cell therapy and related technologies 2008-2018
Table 10-2: Market size according to therapeutic areas for cell therapy 2008-2018
Table 10-3: Cell therapy markets for cardiovascular disorders 2008-2018
Table 10-4: Values of cell therapies for neurological disorders 2008-2018
Table 10-5: Total cell therapy market according to geographical areas 2008-2018
Table 10-6: Cord blood market according to geographical areas 2008-2018
Table 10-7: Stem cells transplant market according to geographical areas 2008-2018
Table 11-1: Publicly traded cell therapy companies
Table 11-2: Selected collaborations of cell therapy companies
Table 12-1: Therapeutic uses of stem cells
Table 12-2: Commercial collaborations of academic institutes in the US relevant to stem cells
Figures
Figure 10-1: Unmet needs in cell therapy
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