Stem Cell and Gene Therapy for Cardiovascular Disease

 
 
Academic Press
  • 1. Auflage
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  • erschienen am 21. August 2015
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  • 538 Seiten
 
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978-0-12-801863-7 (ISBN)
 

Stem Cell and Gene Therapy for Cardiovascular Disease is a state-of-the-art reference that combines, in one place, the breadth and depth of information available on the topic.

As stem cell and gene therapies are the most cutting-edge therapies currently available for patients with heart failure, each section of the book provides information on medical trials from contributors and specialists from around the world, including not only what has been completed, but also what is planned for future research and trials.

Cardiology researchers, basic science clinicians, fellows, residents, students, and industry professionals will find this book an invaluable resource for further study on the topic.


  • Provides information on stem and gene therapy medical trials from contributors and specialists around the world, including not only what has been completed, but also what is planned for future research and trials
  • Presents topics that can be applied to allogeneic cells, mesenchymal cells, gene therapy, cardiomyoctyes, iPS cells, MAPC's, and organogenesis
  • Covers the three areas with the greatest clinical trials to date: chronic limb ischemia, chronic angina, and acute MI
  • Covers the prevailing opinions on how to harness the body's natural repair mechanisms
  • Ideal resource for cardiology researchers, basic science clinicians, fellows, residents, students, and industry professionals
  • Englisch
  • USA
Elsevier Science
  • 53,81 MB
978-0-12-801863-7 (9780128018637)
0128018631 (0128018631)
weitere Ausgaben werden ermittelt
  • Front Cover
  • Stem Cell and Gene Therapy for Cardiovascular Disease
  • Copyright Page
  • Contents
  • List of Contributors
  • Preface
  • Regenerative Medicine and the Cardiovascular System: A Good Start
  • Gene Therapy
  • Tissue Engineering
  • Dedication
  • Acknowledgments
  • References
  • I. Stem Cells
  • 1 Introduction and Overview of Stem Cells
  • What is Regenerative Medicine?
  • What Defines a Stem Cell?
  • Types of Stem Cells
  • Stem Cell Sources
  • Bone Marrow
  • Adipose Tissue
  • Heart-Cardiac Resident Progenitor Cells
  • Somatic (Skin) Cells
  • Umbilical Cord and Placenta
  • Endometrial Tissue
  • Dental Pulp
  • Other Classifications of Stem Cells
  • Autologous versus Allogeneic Cells
  • Multipotent Adult Progenitor Cells
  • Cardiopoiesis-Derived MSCs
  • Mechanisms of Action of Stem Cells
  • Endogenous versus Exogenous Tissue Repair
  • Functional Assays
  • Sex Differences
  • Safety Profile
  • Summary
  • References
  • 2 Pathological Assessment of Experimental Models of Stem Cell and Other Regenerative Therapies
  • Introduction
  • Preparation and Labeling
  • BrdU Incorporation
  • Fluorescence Labeling and Dye Marking
  • Nuclear Dyes
  • Cytoplasmic Dyes
  • Genetic Markers
  • Endogenous Markers
  • Exogenous Markers
  • Delivery Routes for Stem Cells and Other Biological Agents
  • Delivery Through the Vasculature
  • Intramyocardial Delivery
  • Pathologic Assessment
  • Gross Examination
  • Tissue Sampling
  • Triphenyltetrazolium Chloride Staining for Infarct Size Quantification
  • Microscopic Assessment
  • General Evaluation
  • Histologic Findings
  • Cell Characterization
  • Angiogenesis and Capillary Density Assessment
  • Conclusion
  • References
  • 3 Large Animal Models for Cardiac Cell Therapy
  • Introduction
  • Is There a Need for Large Animal Models of Cardiac Diseases?
  • Considerations when Selecting an Animal Model
  • Animal Care: the Ideal is Not Always Easy
  • Physiological Parameters and Data Collection
  • Cardiovascular Anatomy
  • Cardiovascular Physiology
  • Models of Myocardial Ischemia
  • Acute Myocardial Ischemia
  • Coronary Ligation versus Coronary Balloon Occlusion
  • Microsphere Embolization
  • Inorganic Mercury Thrombosis
  • Thrombus
  • Cryothermia
  • Chronic Myocardial Ischemia
  • Ameroid Constrictor
  • Models of Overload
  • Volume Overload
  • Pressure Overload
  • Models of DCM
  • Models of Cardiotoxicity
  • Cell Therapy
  • Bone Marrow Harvest in Porcine Models
  • Delivery of Cell Therapy
  • Open Surgical Transmyocardial Injection
  • Transcatheter Percutaneous Approach
  • Intracoronary and Retrograde Delivery
  • Transmyocardial Injection: Mapping and Injection
  • Conclusions
  • References
  • I. Body's Native Repair Mechanisms
  • 4 Role of Paracrine Mechanisms
  • Introduction and History
  • Identifying Paracrine Factors
  • Paracrine Mechanisms
  • Survival/Cytoprotection
  • Cardiac Remodeling
  • Cardiomyocyte Proliferation
  • Metabolism and Contractility
  • Vascularization
  • Immunomodulation/Inflammation
  • Resident Stem Cell Activation
  • Genetic Engineering of Stem Cells
  • Conclusion
  • References
  • 5 Impact of Telomere Shortening with Age in Stem Cell Therapy: New Strategies to Increase Telomere Length
  • Introduction
  • Telomeres and Aging
  • Aging and Stem Cells
  • Hematopoietic Stem Cells
  • Mesenchymal Stem Cells
  • Cardiac Stem Cells
  • Current Gaps in Our Understanding
  • Antagonizing Stem Cell Aging: Focus on Telomere Length
  • Conclusion
  • Acknowledgment
  • References
  • II. Autologous Bone Marrow
  • 6 Peripheral Arterial Disease
  • Introduction
  • Blood Flow and Circulation to Metabolic Demand
  • Functional Response to Metabolic Demand
  • Ischemia and Impaired Vascular Response
  • Structural Responses to Chronic Ischemia
  • Cell-Based Therapies for Ischemia
  • Unselected Bone Marrow Mononuclear Cells (BM-MNCs)
  • Unselected Peripheral Marrow Mononuclear Cells (PB-MNCs)
  • Unselected BM-MNC and PB MNC
  • Marker Selected Cells
  • Mesenchymal Stem Cells (MSCs)
  • Cell Combination Approaches
  • Additional Considerations for Cell Therapy
  • Cell Origin and Source
  • Cell Dose
  • Administration Route
  • Summary of Cell Therapies
  • Angiogenic Factor Therapies for Ischemia
  • VEGF
  • FGF
  • HGF
  • HIF-1a
  • Del-1
  • Summary of Angiogenic Factors
  • Summary and Conclusion
  • References
  • 7 Cell Therapy for Refractory Angina
  • Introduction
  • Classification of Patients Unsuitable for Revascularization
  • Pathophysiology
  • Stem Cell History and Introduction
  • Clinical Trials
  • Bone Marrow Mononuclear Cells
  • CD34
  • Adipose-Derived Regenerative Cells
  • Meta-Analyses
  • References
  • 8A Stem Cell Therapy for Acute Myocardial Infarction: The European Experience
  • BOOST
  • TOPCARE
  • Leuven AMI Trial
  • ASTAMI
  • REPAIR-AMI
  • Meta-Analyses
  • Possible Reasons for Observed Differences in Outcomes
  • BAMI Trial
  • References
  • 8B Acute Myocardial Infarction: The United States Experience
  • Introduction
  • First Cardiovascular Cell Therapy Patient in the United States
  • First Randomized Cell Therapy Trial in United States following Acute Myocardial Infarction
  • The Studies of the Cardiovascular Cell Therapy Network (CCTRN)
  • The TIME Trial
  • The LateTIME Trial
  • Use of an Allogeneic Cell Product Following Acute Myocardial Infarction
  • Novel Cells for Treatment of STEMI
  • CD34+ Progenitor Cells
  • Multipotent Adult Progenitor Cells (MAPCs)
  • Is the Method of Cell Delivery Important Following AMI?
  • Summary
  • Future Directions
  • References
  • 9 Autologous Bone Marrow Cells for Chronic Ischemic Heart Failure
  • Introduction
  • Clinical Trials of BMCs in Chronic Ischemic Heart Failure
  • Clinical Trials of Discrete Bone Marrow Cell Populations in Chronic Ischemic Heart Failure
  • Future Directions
  • References
  • III. Autologous Adipose Derived Regenerative Cells
  • 10 Adipose-Derived Stem Cells
  • Introduction
  • Criteria for Cells for Cardiovascular Therapy
  • Adipose Tissue Depots
  • Harvest of Lipoaspirate in Coronary Artery Disease (CAD) Patients
  • Cell Isolation
  • Culturing and Differentiation of ASCs
  • Myogenesis into Striated and Smooth Myocytes
  • Chondrogenesis
  • Osteogenesis
  • Adipogenesis
  • Immunophenotype of ASCs
  • Bone Marrow-Derived versus Adipose-Derived Mesenchymal(-like) Stem Cells
  • Working Mechanism of ASCs in CVD
  • Modulation of Cardiomyocyte Survival and Local Immune Response by the Paracrine Action of ASCs
  • ASC Differentiation along Specific Lineage
  • Other Sources of Stem Cells
  • Potential Use of ASCs in the Treatment of Degenerative Disease
  • Preclinical Studies in Animal Models of AMI
  • ASC Therapy in AMI Animal Models
  • ASC Therapy in Animal Models of Congestive Heart Failure
  • The Use of Autologous ASCs in the Treatment of Patients with CVD
  • Conclusions and Future Perspectives
  • References
  • IV. Allogeneic Alternatives to Autologous Bone Marrow: The MSC
  • 11 Mesenchymal Stem Cells
  • Introduction
  • Mesenchymal Stem Cells
  • MSC Therapeutic Activity is Stimulated by Physiological Need
  • MSCs: Off-the-Shelf Biological Inhibitors of Cardiac Inflammation
  • MSCs Inhibiting Cardiomyocyte Death
  • Utilizing Stem Cells for Direct Regeneration of Cardiac Muscle
  • Stem Cell Cardiac Clinical Trials
  • How to Increase Stem Cell Efficacy?
  • Making Stem Cells Home Better
  • Augmentation of Stem Cell Regenerative Activity
  • Conclusion
  • References
  • 12 Allogeneic versus Autologous Source: Comparative Effects
  • Introduction
  • Properties of MSCs
  • Isolation and Expansion of MSCs
  • Multilineage Differentiation Potential
  • Immunomodulatory Effects
  • Paracrine and Pro-Angiogenic Mechanisms
  • Endogenous Cell Stimulation
  • Anti-fibrotic Effects
  • Aging and MSCs
  • Creating the Cell Therapy Product
  • Therapeutic Uses for MSCs
  • Clinical Trials Emerge for Non-Cardiac Disease Processes
  • Preclinical Investigations of Allogeneic versus Autologous MSCs
  • Clinical Trials Using Allogeneic MSCs
  • Cell Combinations
  • Conclusions
  • References
  • 13 Allogeneic Alternatives to Autologous Bone Marrow: The MSC Clinical Trials of Acute MI with MSCs
  • Introduction
  • Immunomodulatory Effects of MSCs
  • Preclinical Data
  • Clinical Trials
  • Conclusions
  • References
  • 14 Allogeneic Alternatives to Autologous Bone Marrow: The MSC Combined Cell Strategies
  • Introduction
  • Biological Basis of Combination Cell Therapy
  • Preclinical Studies
  • Autologous Cell Combinations
  • Xenogeneic Cell Combinations
  • Allogeneic Cell Combinations
  • Clinical Studies
  • Autologous Cell Combinations
  • Allogeneic Cell Combinations
  • Clinical Translation of Cell Combination Therapy
  • Conclusions and Future Directions
  • References
  • 15 Clinical Trials to Date with MSCs: Heart Failure
  • Introduction
  • Clinical Trials of MSCs in Heart Failure
  • Discussion of Clinical Trial Findings
  • Future Perspectives
  • References
  • V. Cardiac Progenitor Cells
  • 16 Therapy with c-kitPOS Cardiac Stem Cells for Ischemic Cardiomyopathy
  • Introduction
  • c-kitPOS CSCs
  • Ontogeny of c-kitPOS CSCs
  • Contribution of c-kitPOS CSCs to Maintenance and Renewal of Myocardium
  • c-kitPOS CSC-Based Therapy for Ischemic Cardiomyopathy
  • Preclinical Animal Models
  • SCIPIO (Cardiac Stem Cell Infusion in Patients with Ischemic Cardiomyopathy) Trial
  • Challenges in c-kitPOS CSC Therapy
  • Poor Survival and Retention of c-kitPOS CSCs Following Transplantation
  • Paucity of Myogenic Differentiation of Transplanted CSCs
  • Conclusions
  • Acknowledgments
  • References
  • 17 Cardiosphere-Derived Cells
  • Cardiosphere-Derived Cells
  • Cell Therapy for Heart Disease
  • Culture Process and CDC Identity
  • CDC Bioactivity
  • CDC Manufacture
  • Clinical Trial Use of CDCs
  • CADUCEUS
  • ALLSTAR
  • DYNAMIC
  • References
  • VI. Other Allogeneic Sources of Stem Cells
  • 18 Cardiovascular Regenerative Cell Therapy Using Umbilical Cord and Endometrial Cells
  • Advantages of Cord Blood
  • Cardiac Angiogenesis Using UCB-Derived HSCs
  • Wharton's Jelly MSC
  • Umbilical Cord Lining Cells
  • Endometrial Regenerative Cells (ERCs)
  • Therapeutic Efficacy of ERC
  • Stem Cell Combinations
  • Conclusion
  • References
  • VII. Genetic Engineering/Cell Transformation
  • 19 Cardiopoietic Stem Cells for Heart Failure Therapy
  • Introduction
  • Regenerative Medicine Paradigm
  • Next-Generation Stem Cell Therapy
  • Progenitor Fitness in Aging and Disease
  • The Basis for Cardiopoiesis
  • Cardiopoiesis in Patient-Derived Stem Cells
  • Clinical Experience
  • Summary
  • References
  • 20 Transformation to Inducible Pluripotent Stem Cells
  • Introduction
  • Factors for Reprogramming with High Efficiency
  • Embryonic Development Associated Transcription Factors
  • Proliferation and Cell Cycle Regulators
  • Epigenetic Modifiers and Small Molecules
  • Microenvironment
  • Sources of Somatic Cells for Reprogramming
  • Delivery Systems
  • Integrating Vectors
  • Retrovirus Transduction
  • Excision of Integrated Reprogramming Factors
  • Non-Integrating Vectors
  • Adenoviral Vectors
  • Sendai Virus Vectors
  • Episomal Vectors
  • Minicircle DNA
  • Non-DNA Reprogramming
  • mRNAs
  • MicroRNAs
  • Recombinant Proteins
  • Applications of Induced Pluripotent Stem Cell-Derived Cardiomyocytes
  • Enriching Cardiomyocyte Differentiation from Pluripotent Stem Cells Using Cytokines and Small Molecules
  • Disease Modeling
  • Long QT Syndrome
  • Hypertrophic Cardiomyopathy
  • Dilated Cardiomyopathy
  • Other Cardiac Diseases
  • Drug Screening
  • Stem Cell Therapy
  • Potential Problems
  • Arrhythmia
  • Tumorigenicity
  • Immunogenicity
  • Conclusions
  • Acknowledgments
  • References
  • 21 Multipotent Adult Progenitor Cells (MAPCs) for Cardiovascular and Neurologic Diseases
  • Introduction
  • Multipotent Adult Progenitor Cells: In Vitro Characterization
  • Rodent MAPC (Renamed in 2012 Rodent BM-Derived Hypoblast Stem Cells (BM-HypoSC))
  • Human MAPC and the Clinical Product MultiStem®
  • Multipotent Adult Progenitor Cells: In Vivo Characterization
  • The Clinical Potential of MAPC/MultiStem® in Ischemic Cardiac Disease
  • The Clinical Potential of MAPC/MultiStem® in Peripheral Vascular Disease
  • The Clinical Potential of MAPC/MultiStem® in Stroke, Traumatic Brain Injury, and Spinal Cord Injury
  • Summary
  • References
  • VIII. Methods of Delivery
  • 22 Intravenous, Intracoronary, Transendocardial, and Advential Delivery
  • General Considerations of Stem Cell Delivery
  • Routes of Cell Delivery
  • Intravascular
  • Intramyocardial
  • Transvascular
  • Intravascular Cell Delivery
  • Intravenous Infusion
  • Intracoronary Delivery
  • Intramyocardial Cell Delivery
  • Transendocardial Injection
  • Transvascular Cell Delivery
  • Advential Delivery
  • Direct Comparisons of Cell Delivery Methods
  • The Future
  • References
  • 23 Retrograde Coronary Sinus Delivery for Cardiac Cell Therapy
  • Anatomy and Complications
  • Technique of Delivery
  • Mechanism of Tissue Delivery
  • Advantages
  • Disadvantages
  • Prehuman Studies
  • Current Clinical Trials
  • Conclusion
  • Epicardial
  • References
  • II. Tissue Engineering
  • 24 Current Perspectives on Methods for Administering Human Pluripotent Stem Cell-Derived Cells for Myocardial Repair
  • Introduction
  • Differentiation of hPSCs into Cardiomyocytes
  • Transplantation Methods
  • Cell Solutions
  • Cell Sheets
  • Scaffolds and Decellularized Tissues
  • Biomaterial Scaffolds
  • Collagen
  • Fibrinogen
  • Alginate
  • Synthetic Scaffolds
  • Polyglycolic Acid
  • Poly e-Caprolactone-co-l-Lactide
  • Polyurethane
  • Engraftment
  • Cell Retention
  • Survival of Transplanted CMs
  • Therapeutic Benefits and Mechanisms of Action
  • Wall Thickness, Stress, and Metabolic Deficiencies
  • Remuscularization
  • Mobilization of Endogenous Cardiac Progenitor Cells
  • Maintenance of Electromechanical Stability
  • Conclusion
  • Acknowledgments
  • References
  • 25 Acellular Injectable Biomaterials for Treating Cardiovascular Disease
  • Introduction
  • Injectable Biomaterials: Mechanisms of Regeneration and Repair
  • Injectable Biomaterial Properties: Engineering Design Criteria for Treating MI and PAD
  • Types of Injectable Biomaterials
  • Injectable Biomaterials Alone: Preclinical and Clinical Applications
  • Natural Biomaterials
  • Collagen
  • Tissue-Derived Extracellular Matrix
  • Fibrin
  • Hyaluronic Acid
  • Alginate
  • Synthetic Biomaterials
  • Injectable Biomaterials for Growth Factor and Small Molecule Delivery
  • Conclusion
  • Acknowledgments
  • Disclosure
  • References
  • 26 Scaffold-Based Cell Delivery for Cardiac Repair
  • Introduction
  • The Optimal Cell Delivery Scaffold for Cardiac Repair
  • Clinical Regulatory Considerations
  • Delivery Approaches
  • Types of Cell Delivery Scaffolds for Cardiac Repair
  • Natural
  • Myocardium
  • Bioengineered Cardiac Matrix
  • Mucosal Tissues
  • Pericardium
  • Serosal Intestinal Submucosa
  • Fibrin
  • Collagen
  • Other Natural Materials
  • Synthetic
  • Poly-glycolic Acid and Poly-lactic Acid
  • Polyurethane
  • Poly(Ethylene Glycol)
  • Other Synthetic Materials
  • Scaffold Delivery Methods
  • Human Trials of Cell-Seeded Scaffolds for Cardiac Repair
  • Conclusion
  • References
  • 27 Biomaterial: Alginate
  • Introduction: Cardiac Pathophysiology of Heart Failure and Alginate as a Potential Therapy
  • Progression from Myocardial Infarction to Chronic Heart Failure
  • Alginate Development
  • Alginate Use for the Prevention of Left Ventricular Dysfunction after an Acute Myocardial Infarction
  • Preclinical Studies
  • First-in-Man Study to Determine Feasibility and Safety of Intracoronary Administration
  • Alginate Scaffolds for the Treatment of Cardiomyopathy
  • Preclinical Studies
  • First in Man Study with Algisyl-LVR for Treatment of Heart Failure
  • Augment-HF Trial
  • Initial Impression of LV Augmentation with Algisyl-LVR
  • Future Directions: Modification of Bioscaffolds with Extracellular Matrix-Derived Functional Groups
  • References
  • 28 Organogenesis
  • Introduction
  • Epidemiology
  • Xenogeneic and Allogeneic Grafts
  • Immunogenicity and Antigen Removal from Tissue Sources
  • Organogenesis
  • Considerations for Cardiac Tissue Engineering
  • Scaffolds
  • Synthetic Materials
  • Biological Materials
  • Decellularization for Organogenesis
  • (Recellularization) Cells
  • Technology for Building Cardiac Constructs
  • 3D Printing
  • Stereolithography
  • Fused Disposition Modeling
  • Bioreactors
  • Preclinical Testing
  • Preclinical Animal Models
  • Heart Valves
  • Pulmonary Valve
  • Aortic Valve
  • Cardiac Patches
  • Whole Heart Replacement
  • Clinical Trials and Guidelines
  • Ethics and Regulation
  • Conclusion
  • References
  • III. Gene Therapy
  • 29 Gene Therapy for Cardiovascular Diseases
  • Introduction
  • Gene Therapy for the Treatment of Heart Failure
  • Gene Delivery Vectors for Cardiac Gene Therapy
  • Nonviral Gene Delivery
  • Viral Vectors
  • Gene Delivery
  • Antegrade Arterial Infusion
  • Retrograde Venous Infusion
  • Aortic Cross Clamping
  • Intravenous Infusion
  • Direct Intramyocardial Injection
  • Pericardial Injection
  • Other Delivery Methods
  • Targets
  • Targeting the ß-Adrenergic System
  • Overexpression of ß-Adrenergic Receptor (ß-AR)
  • Inhibition of G Protein-Coupled Receptor Kinases (GRKs)
  • Activation of Cardiac Adenylyl Cyclase (AC) Expression
  • Targeting Calcium (Ca2+) Cycling Proteins
  • Overexpression of SERCA2a
  • Phospholamban (PLN) Inhibition
  • Active I-1 and Inhibition of PP1
  • S100A1
  • Small Ubiquitin-Like Modifier Type 1(SUMO1)
  • Homing of Stem Cells
  • Clinical Trials
  • Conclusion
  • References
  • 30 SERCA2a Gene Therapy for Heart Failure
  • Introduction
  • Impaired Calcium Cycling in Heart Failure
  • The Beneficial Effect of Potential Therapeutic Strategies in Restoring SR Calcium Uptake
  • Clinical Trials of SERCA2a Gene Transfer
  • Conclusion
  • References
  • 31 SDF-1 for Cardiac Repair
  • SDF-1
  • Early Observations of the Role of SDF-1 in Myocardial Stem Cell Homing
  • Role of SDF-1 in Myocardial Repair
  • SDF-1 in Clinical Heart Failure Studies
  • Relevance of SDF-1 Findings to Tissue Repair
  • Summary
  • References
  • 32 Gene Therapy in Critical Limb Ischemia
  • Introduction
  • The Concepts Underlying Therapeutic Angiogenesis
  • Therapeutic Angiogenesis for CLI
  • Angiogenic Activity and Clinical Efficacy
  • Vascular Endothelial Growth Factor
  • Fibroblast Growth Factor
  • Hypoxia-Inducible Factor
  • Hepatocyte Growth Factor
  • Meta-Analysis of Randomized Trials
  • Safety of Gene Therapy in CLI
  • Future Perspectives
  • References
  • 33 Use of Gene Modified Stem Cells for Acute Myocardial Infarction
  • Strategies to Improve Cell Survival
  • Mesenchymal Stem Cells
  • Endothelial Progenitor Cells
  • Strategies to Foster Differentiation
  • Strategies to Potentiate Migration and Engraftment
  • Mesenchymal Stem Cells
  • Endothelial Progenitor Cells
  • Strategies to Enhance Paracrine Activity
  • Mesenchymal Stem Cells
  • Bone Marrow Mononuclear Cells
  • Strategies to Improve Function of Aged MSCs
  • The ENACT-AMI Clinical Trial
  • Conclusion
  • References
  • IV. Future Directions
  • 34 The History and Future of the Cardiovascular Cell Therapy Research Network
  • Introduction
  • Establishment of the CCTRN
  • Design of Initial CCTRN Studies
  • Implications of the TIME, LateTIME, and FOCUS Trials
  • Establishment of CCTRN-2
  • Accomplishments of CCTRN
  • Innovative Practices of the CCTRN
  • The Future of the CCTRN
  • References
  • 35 Signature of Responders-Lessons from Clinical Samples
  • Introduction
  • Types of Stem Cells Used in CV Therapy
  • Hematopoietic Stem Cells
  • Endothelial Progenitor Cells
  • Mesenchymal Stem Cells
  • Adipose-Derived Stromal/Stem Cells
  • Cardiac Resident Stem Cells
  • Characterizing Stem Cells
  • Cell Function
  • Profiling Cell Types
  • Stem Cells and Their Role in Inflammation
  • The "Niche" Concept of Stem Cells
  • Resident Cardiac Progenitor Cells
  • Cell Profiling and Improving Outcomes in Stem Cell Therapy
  • Sex Differences in Disease and Repair
  • Future Directions
  • References
  • 36 Adjunctive Therapies with LVADs: Combining Biological and Mechanical Regenerative Therapies
  • Introduction and Background: The Case for Combined Regenerative Therapies
  • Clinical Experience of Biologicals in the LVAD Population
  • Characteristics and Complexities of the LVAD Population
  • "Passive" Recovery on LVAD Support
  • Administration of Biologicals in the LVAD Population: More Questions than Answers
  • Defining the Success of Adjunctive Interventions in LVAD Patients
  • Case Study: CTSN LVAD MPC I Trial
  • Early Lessons from Regenerative Biologicals in the LVAD Population and Future Directions
  • References
  • 37 Trials in Non-ischemic Heart Failure
  • Heart Failure and Non-ischemic Dilated Cardiomyopathy
  • Potential Targets for Stem Cell Therapy in Non-ischemic DCM
  • Targeting Cardiomyocytes
  • Viral Etiology
  • Immune Mediated
  • Targeting Extracellular Matrix
  • Cytoskeletal Proteins
  • Vasculature
  • Clinical Trials of Stem Cell Therapy in Non-ischemic DCM
  • Completed Clinical Trials
  • Ongoing Clinical Trials
  • Mechanisms of Action of Stem Cell Therapies in DCM Patients
  • Changes in Myocardial Perfusion
  • Changes in Electroanatomical Properties of the Myocardium
  • Changes in Ventricular Dyssynchrony
  • Conclusions
  • References
  • 38 New Strategies to Enhance Stem Cell Homing for Tissue Repair
  • Introduction
  • Endogenous Stem Cell Homing in Acute Tissue Injury
  • Cell Based Exogenous Repair of Chronic Injury
  • Cell Culture Modifications
  • Cell Preconditioning Strategies
  • Genetic Manipulation
  • Antibodies
  • Physical Cell Preconditioning Strategies
  • Hypoxia
  • Tissue Based Strategies for Chronic Injury
  • Chemokine Overexpression
  • Physical Manipulation
  • Scaffolds and Gels
  • Summary
  • References
  • 39 Cell Therapy in Ischemic Stroke
  • Introduction
  • Stroke: Pathophysiology of Ischemic Injury and Endogenous Repair
  • Cell Types and Sources
  • Mechanisms of Cellular Therapy in Ischemic Stroke Recovery
  • Reducing Local and Systemic Inflammation
  • Neurogenesis and Angiogenesis
  • Enhancing Endogenous Neurogenesis
  • Increased Neural Plasticity
  • Protecting the BBB
  • Preclinical Studies of Cell Therapy in Ischemic Stroke
  • Routes of Cell Delivery
  • Intracerebral (IC)
  • Intra-cisternal/Cerebroventricular (ICV)
  • Intravenous (IV)
  • Intra-arterial (IA)
  • Cell Doses
  • Optimal Time Window for Cell Therapy
  • Clinical Trials of Cell Therapy in Ischemic Stroke
  • Intracerebral Implantation
  • Intra-arterial
  • Intravenous
  • Challenges in Clinical Translation of Cell Therapy in Stroke
  • Challenges in Clinical Trial Design
  • Cell Tracking and Imaging
  • Challenges in Patient Recruitment in Clinical Trials
  • Future Directions: Regulating Stem Cell Research in Cerebrovascular Disease
  • References
  • Index

List of Contributors


Deborah D. Ascheim

International Center for Health Outcomes & Innovation Research (InCHOIR), Department of Population Health Science & Policy, Icahn School of Medicine at Mount Sinai; New York, NY, USA

Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Wayne Balkan,     Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA

Akshay Bareja,     Mandel Center for Hypertension Research and Duke Cardiovascular Research Center, Department of Medicine, Duke University Medical Center, Durham, USA

Courtney E. Bartlett,     Division of Cardio-Thoracic Surgery, Department of Surgery, University of Utah, Salt Lake City, UT, USA

Atta Behfar,     Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, USA

Lisle Blackbourn,     Division of Cardiovascular Medicine, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

Roberto Bolli,     Institute of Molecular Cardiology, Division of Cardiovascular Medicine, Department of Medicine, University of Louisville, Louisville, KY, USA

L. Maximilian Buja

Cardiovascular Pathology Research Department, Texas Heart Institute, Houston, TX, USA

Department of Pathology and Laboratory Medicine, the University of Texas Health Science Center at Houston, TX, USA

Angela Castellanos,     Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA

Antoine H. Chaanine,     Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, USA

Eric Chau,     Texas Heart Institute, Department of Regenerative Medicine Research, Houston, TX, USA

Zhen Chen,     Department of Medicine, UC San Diego, San Diego, CA, USA

Karen L. Christman

Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA

Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA

Amy Chung,     NeoStem, Inc., New York, NY, USA

Robert M. Cole,     Cedars-Sinai Heart Institute, Los Angeles, CA, USA

John P. Cooke,     Houston Methodist Research Institute, Houston, TX, USA

H.J. Duckers,     Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands

Victor J. Dzau,     Mandel Center for Hypertension Research and Duke Cardiovascular Research Center, Department of Medicine, Duke University Medical Center, Durham, USA

Ray F. Ebert,     National Institutes of Health/National Heart, Lung, and Blood Institute, Bethesda, MD, USA

Jun Fujita,     Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

Keiichi Fukuda,     Department of Cardiology, Keio University School of Medicine, Tokyo, Japan

Roberto Gaetani

Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA

Sanford Consortium for Regenerative Medicine, La Jolla, CA, USA

Amir Gahremanpour,     Stem Cell Center and Adult Cardiology, Texas Heart Institute, Houston, TX, USA

W. Gathier,     Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands

Annetine C. Gelijns,     International Center for Health Outcomes & Innovation Research (InCHOIR), Department of Population Health Science & Policy, Icahn School of Medicine at Mount Sinai; New York, NY, USA

Andrea S. Gobin,     Texas Heart Institute, Department of Regenerative Medicine Research, Houston, TX, USA

José A. Gomez,     Mandel Center for Hypertension Research and Duke Cardiovascular Research Center, Department of Medicine, Duke University Medical Center, Durham, USA

Roger J. Hajjar,     Cardiovascular Research Center, Mount Sinai School of Medicine, New York, NY, USA

Joshua M. Hare,     Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA

Nirmala Hariharan,     Department of Pharmacology, University of California Davis, Davis, CA, USA

Timothy D. Henry,     Cedars-Sinai Heart Institute, Los Angeles, CA, USA

William Hiesinger,     Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA

Alan T. Hirsch,     University of Minnesota Medical School, Minneapolis, MN, USA

Conrad P. Hodgkinson,     Mandel Center for Hypertension Research and Duke Cardiovascular Research Center, Department of Medicine, Duke University Medical Center, Durham, USA

Kimberly N. Hong,     Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA

Kyung U. Hong,     Institute of Molecular Cardiology, Division of Cardiovascular Medicine, Department of Medicine, University of Louisville, Louisville, KY, USA

Thomas E. Ichim,     Institute for Molecular Medicine, Huntington Beach, CA, USA

E. Marc Jolicoeur,     Montreal Heart Institute, Université de Montréal, Montréal, Québec, Canada

Kazuki Kodo

Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA

Department of Medicine, Division of Cardiology, Stanford University, Stanford, CA, USA

Sandeep K. Krishnan,     Cedars-Sinai Heart Institute, Los Angeles, CA, USA

Michael J.B. Kutryk,     Interventional Cardiology Research, St. Michael's Hospital; Department of Medicine, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada

David S. Lee,     Department of Medicine, University of California San Francisco, San Francisco, CA

Randall J. Lee

Department of Medicine, University of California San Francisco, San Francisco, CA

Cardiovascular Research Center, University of California San Francisco, San Francisco, CA

Institute for Regeneration Medicine, University of California San Francisco, San Francisco, CA

Division of Cardiology, Section of Cardiac Electrophysiology, University of California, San Francisco, CA

Douglas W. Losordo,     NeoStem, Inc., New York, NY, USA

Elton Migliati,     Texas Heart Institute, Houston, TX, USA

Leslie W. Miller,     Visiting Research and Clinical Consultant, Texas Heart Institute, Houston, TX, USA

Vivek Misra,     The University of Texas Health Science Center at San Antonio, Texas, USA

Lem Moyé,     University of Texas School of Public Health, Houston, TX, USA

Nathalie Nguyen,     Department of Biology, San Diego State University, San Diego, CA, USA

Sang-Ging Ong

Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA

Department of Medicine, Division of Cardiology, Stanford University, Stanford, CA, USA

Aaron Orozco,     Texas Heart Institute, Department of Regenerative Medicine Research, Houston, TX, USA

Amit N. Patel,     Division of Cardio-Thoracic Surgery, Department of Surgery, University of Utah, Salt...

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