Stem Cell and Gene Therapy for Cardiovascular Disease

1st Edition - August 21, 2015
Editors: Emerson c. Perin, Leslie W. Miller, Doris Taylor, James T. Willerson
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 0 1 8 8 8 - 0
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 0 1 8 6 3 - 7

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. A… Read more

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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.

List of Contributors
Preface
Regenerative Medicine and the Cardiovascular System: A Good Start
- Gene Therapy
- Tissue Engineering
- Dedication
- Acknowledgments
- References
Part I: Stem Cells
- Chapter 1. Introduction and Overview of Stem Cells
  - What is Regenerative Medicine?
  - What Defines a Stem Cell?
  - Summary
  - References
- Chapter 2. Pathological Assessment of Experimental Models of Stem Cell and Other Regenerative Therapies
  - Introduction
  - Preparation and Labeling
  - Delivery Routes for Stem Cells and Other Biological Agents
  - Pathologic Assessment
  - Conclusion
  - References
- Chapter 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
  - Models of Myocardial Ischemia
  - Models of Overload
  - Models of DCM
  - Models of Cardiotoxicity
  - Cell Therapy
  - Bone Marrow Harvest in Porcine Models
  - Delivery of Cell Therapy
  - Conclusions
  - References
- Section I: Body’s Native Repair Mechanisms
  - Chapter 4. Role of Paracrine Mechanisms
    - Introduction and History
    - Identifying Paracrine Factors
    - Paracrine Mechanisms
    - Genetic Engineering of Stem Cells
    - Conclusion
    - References
  - Chapter 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
    - Current Gaps in Our Understanding
    - Antagonizing Stem Cell Aging: Focus on Telomere Length
    - Conclusion
    - Acknowledgment
    - References
- Section II: Autologous Bone Marrow
  - Chapter 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
  - Chapter 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
  - Chapter 8A. Stem Cell Therapy for Acute Myocardial Infarction: The European Experience
    - BOOST
    - TOPCARE
    - ASTAMI
    - REPAIR-AMI
    - Possible Reasons for Observed Differences in Outcomes
    - BAMI Trial
    - References
  - Chapter 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
    - Multipotent Adult Progenitor Cells (MAPCs)
    - Is the Method of Cell Delivery Important Following AMI?
    - Summary
    - Future Directions
    - References
  - Chapter 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
- Section III: Autologous Adipose Derived Regenerative Cells
  - Chapter 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
    - Immunophenotype of ASCs
    - Bone Marrow-Derived versus Adipose-Derived Mesenchymal(-like) Stem Cells
    - Working Mechanism of ASCs in CVD
    - Potential Use of ASCs in the Treatment of Degenerative Disease
    - Conclusions and Future Perspectives
    - References
- Section IV: Allogeneic Alternatives to Autologous Bone Marrow: The MSC
  - Chapter 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?
    - Conclusion
    - References
  - Chapter 12. Allogeneic versus Autologous Source: Comparative Effects
    - Introduction
    - Properties of MSCs
    - Therapeutic Uses for MSCs
    - Cell Combinations
    - Conclusions
    - References
  - Chapter 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
  - Chapter 14. Allogeneic Alternatives to Autologous Bone Marrow: The MSC Combined Cell Strategies
    - Introduction
    - Biological Basis of Combination Cell Therapy
    - Preclinical Studies
    - Clinical Studies
    - Clinical Translation of Cell Combination Therapy
    - Conclusions and Future Directions
    - References
  - Chapter 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
- Section V: Cardiac Progenitor Cells
  - Chapter 16. Therapy with c-kit^POS Cardiac Stem Cells for Ischemic Cardiomyopathy
    - Introduction
    - c-kit^POS CSCs
    - Ontogeny of c-kit^POS CSCs
    - Contribution of c-kit^POS CSCs to Maintenance and Renewal of Myocardium
    - c-kit^POS CSC-Based Therapy for Ischemic Cardiomyopathy
    - Challenges in c-kit^POS CSC Therapy
    - Conclusions
    - Acknowledgments
    - References
  - Chapter 17. Cardiosphere-Derived Cells
    - Cardiosphere-Derived Cells
    - References
- Section VI: Other Allogeneic Sources of Stem Cells
  - Chapter 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
- Section VII: Genetic Engineering/Cell Transformation
  - Chapter 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
  - Chapter 20. Transformation to Inducible Pluripotent Stem Cells
    - Introduction
    - Factors for Reprogramming with High Efficiency
    - Sources of Somatic Cells for Reprogramming
    - Delivery Systems
    - Applications of Induced Pluripotent Stem Cell-Derived Cardiomyocytes
    - Conclusions
    - Acknowledgments
    - References
  - Chapter 21. Multipotent Adult Progenitor Cells (MAPCs) for Cardiovascular and Neurologic Diseases
    - Introduction
    - Multipotent Adult Progenitor Cells: In Vitro Characterization
    - Multipotent Adult Progenitor Cells: In Vivo Characterization
    - Summary
    - References
- Section VIII: Methods of Delivery
  - Chapter 22. Intravenous, Intracoronary, Transendocardial, and Advential Delivery
    - General Considerations of Stem Cell Delivery
    - Routes of Cell Delivery
    - Intravascular Cell Delivery
    - Intramyocardial Cell Delivery
    - Transvascular Cell Delivery
    - Direct Comparisons of Cell Delivery Methods
    - The Future
    - References
  - Chapter 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
Part II: Tissue Engineering
- Chapter 24. Current Perspectives on Methods for Administering Human Pluripotent Stem Cell-Derived Cells for Myocardial Repair
  - Introduction
  - Differentiation of hPSCs into Cardiomyocytes
  - Transplantation Methods
  - Engraftment
  - Therapeutic Benefits and Mechanisms of Action
  - Maintenance of Electromechanical Stability
  - Conclusion
  - Acknowledgments
  - References
- Chapter 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
  - Injectable Biomaterials for Growth Factor and Small Molecule Delivery
  - Conclusion
  - Acknowledgments
  - Disclosure
  - References
- Chapter 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
  - Conclusion
  - References
- Chapter 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
  - First in Man Study with Algisyl-LVR for Treatment of Heart Failure
  - Augment-HF Trial
  - Future Directions: Modification of Bioscaffolds with Extracellular Matrix-Derived Functional Groups
  - References
- Chapter 28. Organogenesis
  - Introduction
  - Considerations for Cardiac Tissue Engineering
  - Heart Valves
  - Cardiac Patches
  - Whole Heart Replacement
  - Clinical Trials and Guidelines
  - Ethics and Regulation
  - Conclusion
  - References
Part III: Gene Therapy
- Chapter 29. Gene Therapy for Cardiovascular Diseases
  - Introduction
  - Gene Therapy for the Treatment of Heart Failure
  - Gene Delivery Vectors for Cardiac Gene Therapy
  - Gene Delivery
  - Targets
  - Clinical Trials
  - Conclusion
  - References
- Chapter 30. SERCA2a Gene Therapy for Heart Failure
  - Introduction
  - Impaired Calcium Cycling in Heart Failure
  - Conclusion
  - References
- Chapter 31. SDF-1 for Cardiac Repair
  - SDF-1
  - Role of SDF-1 in Myocardial Repair
  - SDF-1 in Clinical Heart Failure Studies
  - Summary
  - References
- Chapter 32. Gene Therapy in Critical Limb Ischemia
  - Introduction
  - The Concepts Underlying Therapeutic Angiogenesis
  - Angiogenic Activity and Clinical Efficacy
  - Fibroblast Growth Factor
  - Hypoxia-Inducible Factor
  - Hepatocyte Growth Factor
  - Meta-Analysis of Randomized Trials
  - Safety of Gene Therapy in CLI
  - Future Perspectives
  - References
- Chapter 33. Use of Gene Modified Stem Cells for Acute Myocardial Infarction
  - Strategies to Improve Cell Survival
  - Strategies to Foster Differentiation
  - Strategies to Potentiate Migration and Engraftment
  - Strategies to Enhance Paracrine Activity
  - Strategies to Improve Function of Aged MSCs
  - The ENACT-AMI Clinical Trial
  - Conclusion
  - References
Part IV: Future Directions
- Chapter 34. The History and Future of the Cardiovascular Cell Therapy Research Network
  - Introduction
  - Establishment of the CCTRN
  - Establishment of CCTRN-2
  - Accomplishments of CCTRN
  - References
- Chapter 35. Signature of Responders—Lessons from Clinical Samples
  - Introduction
  - Types of Stem Cells Used in CV Therapy
  - Characterizing Stem Cells
  - Stem Cells and Their Role in Inflammation
  - The “Niche” Concept of Stem Cells
  - Cell Profiling and Improving Outcomes in Stem Cell Therapy
  - Sex Differences in Disease and Repair
  - Future Directions
  - References
- Chapter 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
- Chapter 37. Trials in Non-ischemic Heart Failure
  - Heart Failure and Non-ischemic Dilated Cardiomyopathy
  - Potential Targets for Stem Cell Therapy in Non-ischemic DCM
  - Clinical Trials of Stem Cell Therapy in Non-ischemic DCM
  - Mechanisms of Action of Stem Cell Therapies in DCM Patients
  - Conclusions
  - References
- Chapter 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
  - Physical Cell Preconditioning Strategies
  - Tissue Based Strategies for Chronic Injury
  - Summary
  - References
- Chapter 39. Cell Therapy in Ischemic Stroke
  - Introduction
  - Mechanisms of Cellular Therapy in Ischemic Stroke Recovery
  - Preclinical Studies of Cell Therapy in Ischemic Stroke
  - Clinical Trials of Cell Therapy in Ischemic Stroke
  - Intracerebral Implantation
  - Challenges in Clinical Translation of Cell Therapy in Stroke
  - Future Directions: Regulating Stem Cell Research in Cerebrovascular Disease
  - References
Index

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Stem Cell and Gene Therapy for Cardiovascular Disease

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Emerson c. Perin

Leslie W. Miller

Doris Taylor

James T. Willerson