Regenerative Medicine Applications in Organ Transplantation - 1st Edition - ISBN: 9780123985231, 9780123985200

Regenerative Medicine Applications in Organ Transplantation

1st Edition

Editors: Giuseppe Orlando
Hardcover ISBN: 9780123985231
eBook ISBN: 9780123985200
Imprint: Academic Press
Published Date: 5th November 2013
Page Count: 1050
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Regenerative Medicine Applications in Organ Transplantation illustrates exactly how these two fields are coming together and can benefit one another. It discusses technologies being developed, methods being implemented, and which of these are the most promising. The text encompasses tissue engineering, biomaterial sciences, stem cell biology, and developmental biology, all from a transplant perspective. Organ systems considered include liver, renal, intestinal, pancreatic, and more. Leaders from both fields have contributed chapters, clearly illustrating that regenerative medicine and solid organ transplantation speak the same language and that both aim for similar medical outcomes. The overall theme of the book is to provide insight into the synergy between organ transplantation and regenerative medicine.

Recent groundbreaking achievements in regenerative medicine have received unprecedented coverage by the media, fueling interest and enthusiasm in transplant clinicians and researchers. Regenerative medicine is changing the premise of solid organ transplantation, requiring transplantation investigators to become familiar with regenerative medicine investigations that can be extremely relevant to their work. Similarly, regenerative medicine investigators need to be aware of the needs of the transplant field to bring these two fields together for greater results.

Key Features

  • Bridges the gap between regenerative medicine and solid organ transplantation and highlights reasons for collaboration
  • Explains the importance and future potential of regenerative medicine to the transplant community
  • Illustrates to regenerative medicine investigators the needs of the transplant discipline to drive and guide investigations in the most promising directions


Basic and clinical researchers in the fields of regenerative medicine, transplantation, tissue engineering, biomaterial sciences, stem cell biology, developmental biology, and related fields

Table of Contents


Meet the Editors

List of Contributors

Preface: Solid Organ Transplantation in the Regenerative Medicine Era

Chapter 1. Introduction: Regenerative Medicine and Solid Organ Transplantation from a Historical Perspective

1.1 Introduction

1.2 Major Advances in Organ Transplantation

1.3 Regenerative Medicine


Chapter 2. Solid Organ Transplantation: Has the Promise Been Kept and the Needs Met?

2.1 Introduction

2.2 Tolerance in organ transplantation

2.3 Organ shortage

2.4 Conclusions


Part I: Principles of Regenerative Medicine and Cell, Tissue, and Organ Bioengineering

Chapter 3. Strategies for the Specification of Tissue Engineering Biomaterials

3.1 Introduction: the Engineering Approach to Tissue Regeneration

3.2 Principles of Biomaterials Selection in Tissue Engineering

3.3 Specific Types of Template Material

3.4 Concluding Comments

Author’s Note


Chapter 4. Principles of Stem Cell Biology

4.1 The Origin of the Cell Reprogramming

4.2 Somatic Cell Nuclear Transfer

4.3 Cell Fusion

4.4 Transcription Factor Transduction: iPS Cell Generation

4.5 Novelty in Nuclear Reprogramming

4.6 Comparison Between the Three Approaches of Nuclear Reprogramming

4.7 Conclusions


Chapter 5. Principles of Cell Sheet Technology

5.1 Introduction

5.2 Functional Tissue Regeneration Using Cell Sheets

5.3 Conclusions



Chapter 6. Principles of Bioprinting Technology

6.1 Introduction

6.2 Bio-blueprint

6.3 Bio-ink

6.4 Bio-Paper

6.5 Organ Bio-Printers and Bioprinting Methods

6.6 Summary



Chapter 7. Synthetic Biomaterials for Regenerative Medicine Applications

7.1 Introduction

7.2 Biologically Relevant Properties of Polymeric Biomaterials

7.3 Classic Materials

7.4 Degradable Polymers

7.5 Hydrogels

7.6 Summary and Future Directions


Chapter 8. Natural Biomaterials for Regenerative Medicine Applications

8.1 Introduction

8.2 ECM Composition and Tissue-Specific Ultrastructure

8.3 Production of Naturally Occurring Biomaterials from Decellularized Tissues

8.4 Mechanisms by Which Biomaterials Support Constructive Remodeling


Chapter 9. Bioartificial Biomaterials for Regenerative Medicine Applications

9.1 Relevance of Bioartificial Materials in Regenerative Medicine

9.2 Different Levels of Biomimickry in Bioartificial Materials

9.3 Bioartificial Materials by Blending

9.4 Bioartificial Hydrogels

9.5 Bioartificial Materials Through Coating Strategies

9.6 Conclusions and Future Perspective



Chapter 10. Bioactivated Materials for Cell and Tissue Guidance

10.1 Introduction

10.2 Evolution of Scaffold Design Concept

10.3 Bioactivated Programmable Cell-Instructive Scaffolds

10.4 Conclusion and Remarks


Chapter 11. Biocompatibility and Immune Response to Biomaterials

11.1 Introduction

11.2 Transplant Rejection

11.3 The Host Response to Tissue Injury

11.4 The Foreign Body Reaction

11.5 Macrophage Polarization

11.6 The Host Response to ECM-Based Scaffolds

11.7 Conclusion


Chapter 12. Harnessing Regenerative and Immunomodulatory Properties of Mesenchymal Stem Cells in Transplantation Medicine

12.1 Introduction

12.2 Use of MSCs in Hematopoietic Stem Cell Transplantation

12.3 Use of MSCs in Non-HSC Transplant Settings

12.4 Role of MSCs in Solid Organ Transplantation

12.5 Practical Issues

12.6 Evolving Concepts

12.7 Conclusions


Chapter 13. Bioreactors for Tissue Engineering Purposes

13.1 Mixing Bioreactors

13.2 Guiding Tissue Structure and Function

13.3 Conclusion


Part II: Kidney

Chapter 14. Current Status of Renal Transplantation

14.1 The Waiting List

14.2 Donation

14.3 Outcomes

14.4 Causes of Graft Loss

14.5 Mechanisms of Rejection

14.6 Expanding the Deceased Donor Organ Pool

14.7 Expanded Criteria Donors

14.8 Donation After Cardiac Death

14.9 Dual Kidney Transplants

14.10 Centers for Disease Control and Prevention High-Risk Kidneys

14.11 Pediatric Kidneys

14.12 Kidneys from Donors with Acute Renal Failure

14.13 Living Donation

14.14 Immunosuppression: Current Status and Emerging Therapies

14.15 Progress Toward Tolerance

14.16 New Kidney Allocation Policy Proposal in the United States

14.17 Conclusion


Chapter 15. Living Donor Renal Transplantation: Progress, Pitfalls, and Promise

15.1 Introduction

15.2 The Donor Operation

15.3 Perioperative Risks of Living Donor Nephrectomy

15.4 Potential Problems with Living Donors

15.5 Outcomes After LDT

15.6 Problems with LDT

15.7 HLA-Incompatible Transplantation

15.8 Blood Group Incompatible Transplantation

15.9 Alternatives to Antibody-Incompatible Transplantation

15.10 Future Directions in Living Donor Transplantation

15.11 Conclusion


Chapter 16. Machine Perfusion of Kidneys Donated After Circulatory Death: The Carrel and Lindbergh Legacy

16.1 Introduction

16.2 Concept of Machine Perfusion

16.3 Machine Perfusion Introduced in the Clinics

16.4 Machine Perfusion Disappears to the Background

16.5 Machine Preservation Revival

16.6 What is the Evidence?

16.7 Machine Perfusion in the Twenty-First Century—Active Organ Repair During Machine Perfusion

16.8 Conclusions


Chapter 17. Renal Regeneration: The Bioengineering Approach

17.1 Introduction

17.2 Overview of Organ Bioengineering

17.3 Kidney ECM

17.4 ECM in Renal Bioengineering: Bioartificial Scaffolds

17.5 ECM in Renal Bioengineering: Native ECM

17.6 Organ Bioengineering and Regeneration Technology: Moving Forward

17.7 Conclusion


Chapter 18. Renal Regeneration: The Stem Cell Biology Approach

18.1 Introduction

18.2 Acute Kidney Failure

18.3 Stem Cells and AKF

18.4 Chronic Renal Diseases

18.5 Stem Cells and CKD

18.6 Conclusion


Chapter 19. Renal Regeneration: The Developmental Approach

19.1 Normal Kidney Development

19.2 Modeling Developmental Programs Using Organ Culture

19.3 Modeling Renal Morphogenesis with Modified Organ Cultures

19.4 Tissue Engineering

19.5 Ex Vivo/In Vivo Approaches

19.6 Cell-Based Approaches

19.7 Conclusion


Part III: Liver

Chapter 20. Current Status of Liver Transplantation

20.1 Historical Note

20.2 The Status in 1983

20.3 The Status 30 Years Later…

20.4 Indications for LT in the Twenty-First Century




Chapter 21. Living-Related Liver Transplantation: Progress, Pitfalls, and Promise

21.1 Historical Note

21.2 Actual Status: Eastern Versus Western Experiences

21.3 Controversial Issues

21.4 Technical Challenges and Controversies

21.5 Recipient Morbidity and Mortality

21.6 Donor Morbidity and Mortality

21.7 Conclusion



Chapter 22. Donation After Cardiac Death in Liver Transplantation

22.1 Introduction

22.2 Classification of DCD

22.3 DCD Liver Transplantation: The Past, a Historical Perspective

22.4 DCD Liver Transplantation: The Present

22.5 Conclusions


Chapter 23. Artificial Liver Support

23.1 Introduction

23.2 Liver Support Techniques

23.3 Future Perspectives and Conclusions


Chapter 24. Liver Regeneration: The Bioengineering Approach

24.1 Introduction

24.2 Development of BAL Devices

24.3 Engineering Perspective on Hepatocyte Transplantation

24.4 Hepatic Tissue Engineering

24.5 Whole Liver Tissue Engineering

24.6 Conclusion


Chapter 25. Liver Regeneration: The Developmental Biology Approach

25.1 Introduction

25.2 Historical Perspectives

25.3 Experimental Models of Liver Regeneration

25.4 General Principles of Liver Regeneration

25.5 Molecular Regulation of Liver Regeneration

25.6 Clinical Implications

25.7 Summary and Areas of Future Investigation

25.8 Acknowledgments


Chapter 26. Liver Regeneration: The Stem Cell Approach

26.1 Liver Structure and Function

26.2 Animal Models of Liver Regeneration

26.3 Regeneration of Liver Cell Subpopulations

26.4 Extrahepatic Liver Cell Progenitors

26.5 Isolation and Identification of Extra-HPCs

26.6 Transplantable Cells that Repopulate the Liver—Potential for Cell Therapy

26.7 Conclusion and Future Directions


Chapter 27. Liver Regeneration and Bioengineering: The Role of Liver Extra-Cellular Matrix and Human Stem/Progenitor Cells

27.1 Liver Development and the Stem Cell Niche

27.2 The Liver ECM

27.3 The Liver Stem Cells and Matrix Mechanobiology

27.4 Cellular Therapies for Liver Disease

27.5 Augmentation of Cell Therapies by Natural ECM

27.6 Bioengineering of Livers Using Liver ECM as a Scaffold


Part IV: Heart

Chapter 28. Current Status of Heart Transplantation

28.1 The Heart Failure Syndrome

28.2 Cardiac Transplantation: Historical Achievement

28.3 Heart Transplant Evaluation

28.4 Listing Status

28.5 The Ideal Donor Heart

28.6 Perioperative Management

28.7 Immunosuppression Strategies and Rejection Surveillance

28.8 Maintenance Immunosuppression

28.9 Rejection Surveillance

28.10 Transplantation Outcomes

28.11 Mechanical Horizon: VADs as a Bridge to Transplant

28.12 Future Directions in Cardiac Transplantation

28.13 Conclusion



Chapter 29. Artificial Heart Support

29.1 Introduction

29.2 Definition

29.3 History of Research on VADs and TAH

29.4 Indications for MCS

29.5 Types of MCS Systems

29.6 Patient Selection and Timing of Implant

29.7 Surgical Procedure for Implantable VADs and Postoperative Management

29.8 Long-Term Outcome of Implantable VADs

29.9 Future Perspectives


Chapter 30. Heart Regeneration: The Bioengineering Approach

30.1 Introduction

30.2 Acellular Approaches

30.3 Cell-Based Approaches: Non-injectable Materials

30.4 Injectable Materials

30.5 Hydrogel Scaffolds with Controlled Mechanical Properties

30.6 Donor-to-Host Integration

30.7 Future Considerations


Chapter 31. Heart Regeneration: The Developmental and Stem Cell Biology Approach

31.1 Introduction

31.2 Cardiac Developmental Biology

31.3 Innate Cardiac Regeneration

31.4 Clinical Strategies to Augment Cardiac Regeneration

31.5 Conclusions


Part V: Small Bowel

Chapter 32. Current Status of Intestinal Transplantation

32.1 Introduction

32.2 Diagnoses and Indications for Intestinal Transplant

32.3 Intestinal Rehabilitation

32.4 Types of Intestinal Grafts

32.5 Surgical Procedure

32.6 Immunosuppression

32.7 Monitoring of the Graft

32.8 Complications

32.9 Results

32.10 Conclusions


Chapter 33. Living Related Small Bowel Transplantation: Progress, Pitfalls, and Promise

33.1 Donor

33.2 Recipient

33.3 Current Status of Intestine Transplantation

33.4 Regenerative Medicine in Organ Transplantation


Chapter 34. Intestinal Regeneration: The Bioengineering Approach

34.1 Introduction to the Enteric Nervous System

34.2 Disorders of the ENS and Current Therapeutic Paradigms

34.3 Tissue Engineering of the Intestinal Neuromusculature

34.4 Sources of Smooth Muscle and Neuronal Stem and Progenitor Cells

34.5 A Summary of Delivery Strategies for NSCs in the GI Tract

34.6 Smooth Muscle Intestinal Tissue Engineering

34.7 Future Perspectives



Chapter 35. Intestinal Regeneration: The Developmental Biology Approach

35.1 The Molecular Basis of Organogenesis

35.2 Embryological Organogenesis

35.3 Regenerative Organogenesis

35.4 Alternative Animal Models

35.5 Concluding Remarks


Chapter 36. Intestinal Regeneration: The Stem Cell Approach

36.1 Introduction

36.2 Tissue Engineering of the Intestinal Tract

36.3 Transition to an In Vivo Model

36.4 Engineered Intestine Is Distinct from Healing, Tissue Transfer, and Monolayer Cell Culture

36.5 Organoid Unit Approach Facilitates Engineering of the Gastrointestinal Tract

36.6 Nutrient Supply to the Neoorgan

36.7 Cell Signaling

36.8 Defining the Progenitor Cells of the Intestine

36.9 The Stem Cell Niche

36.10 Intestine Regeneration Using Stem Cells: TESI


Chapter 37. Building Blocks for Engineering the Small Intestine

37.1 Recent Advances in Intestinal Tissue Engineering

37.2 Current Understanding of ISC Biology

37.3 Advances in In Vitro Expansion of Intestinal Epithelium

37.4 Concluding Remarks


Part VI: Endocrine Pancreas and Islets of Langerhans

Chapter 38. Current Status of Pancreas Transplantation

38.1 Importance of Glycemic Control

38.2 Hypercoagulable State in T1D/ESRD

38.3 Pancreas Transplant, Technical Aspects

38.4 Immunosuppression in PT

38.5 PT: Patient, Pancreas, and Kidney Transplant Survival

38.6 PT: Impact on Diabetes-Related Complications

38.7 T1D Recurrence after PT

38.8 Challenges and Future Perspectives in PT



Chapter 39. Living-Donor Pancreas Transplantation: Progress, Pitfalls, and Promise

39.1 Introduction

39.2 Rationale for Pancreas Transplants

39.3 Rationale for LD Pancreas Transplants

39.4 The Donor

39.5 The Recipient

39.6 The Identical-Twin Experience

Author Contributions



Chapter 40. Current Status of Islet Transplantation

40.1 Introduction

40.2 The Burden of Type 1 Diabetes Mellitus

40.3 Pathophysiology of Type 1 Diabetes Mellitus

40.4 Standard Management of Patients with Type 1 Diabetes

40.5 Indications to Islet Transplantation

40.6 The Origins of Islet Transplantation

40.7 Clinical Outcomes of Islet Transplantation

40.8 Immunosuppressive Regimens for Islet Transplantation

40.9 Future Developments

40.10 Conclusion


Chapter 41. Pancreatic Islets Regeneration: The Bioengineering Approach

41.1 Introduction

41.2 Islet Encapsulation

41.3 The Importance of the Pancreatic Extracellular Matrix

41.4 Decellularization–Recellularization Technology

41.5 Whole-Organ Pancreas Bioengineering

41.6 Future Challenges


Chapter 42. Pancreatic Islet Regeneration: The Developmental and Stem Cell Biology Approach

42.1 Introduction

42.2 Embryonic Development of Pancreas and Islets

42.3 Recapitulating Development: Strategies for β-Cell Differentiation

42.4 Stem Cells and Progenitors for the β-Cell Phenotype

42.5 miRNA and siRNA in Differentiation

42.6 Challenges and Perspectives


Chapter 43. Microencapsulation Technology

43.1 Introduction

43.2 Islet Isolation

43.3 Alginate-Based Microencapsulation of Islets

43.4 Potential Role of ECM-Based Technology in the Development of the BAP

43.5 Conclusions



Chapter 44. Autologous Islets Transplantation

44.1 Introduction

44.2 Background

44.3 Patient Selection and Surgical Considerations

44.4 Islet Isolation and Intraportal Infusion

44.5 Sites for Islet Engraftment

44.6 IAT Results

44.7 Complications of TP-IAT

44.8 Unsuccessful IAT: Salvage by Allogeneic Pancreas Transplantation

44.9 What Do the Results of IAT Mean for Allogeneic Islet Transplantation?

44.10 Summary


Part VII: Lung

Chapter 45. Current Status of Lung Transplantation

45.1 Introduction

45.2 History of LTx

45.3 Current Activities Worldwide

45.4 Indications

45.5 Recipient Selection

45.6 Timing of Listing and Organ Allocation

45.7 Transplant Procedure

45.8 Donor Types, Selection, and Management

45.9 Lung Preservation Techniques

45.10 Results

45.11 Complications and Morbidities

45.12 Experience with LTx at the University Hospitals Leuven

45.13 Conclusions and Future Directions



Chapter 46. Living Related Lung Transplantation: Progress, Pitfalls, and Promise

46.1 History and Concept

46.2 Patient Selection

46.3 Donor Selection

46.4 Size Matching

46.5 Surgical Technique

46.6 LDLLT Using Oversized Graft

46.7 LDLLT Using Undersized Graft

46.8 Postoperative Management

46.9 Outcome of Living Donors

46.10 Outcome of LDLLT Recipient

46.11 LDLLT for IP

46.12 LDLLT for Bronchiolitis Obliterans

46.13 LDLLT for PH

46.14 Comparison with CLT


Chapter 47. Artificial Lung Support

47.1 Introduction

47.2 Indications and Contraindications for ECLS

47.3 New Technology

47.4 Modes of ECLS—Configuration of Device

47.5 Clinical Management

47.6 Conclusions and Future of ECLS


Chapter 48. Lung Regeneration: The Bioengineering Approach

48.1 Introduction

48.2 Scaffolds for Lung Engineering

48.3 Potential Cell Sources for Lung Engineering

48.4 Engineering of Lung Tissue

48.5 Conclusions


Chapter 49. Lung Regeneration: The Developmental Biology Approach

49.1 Introduction

49.2 Overview of Lung Development

49.3 Cell Signaling in Lung Development

49.4 Endogenous Airway Homeostasis

49.5 Airway Regeneration Following Injury

49.6 Cell Signaling in the Adult Airway Epithelium

49.7 Generation of Airway Cells from Pluripotent Cells Using a Developmental Approach

49.8 Airway Tissue Engineering


Chapter 50. Lung Regeneration: The Stem Cell Approach

50.1 Lung Stem/Progenitor Cells and Differentiated Cells

50.2 Lung Differentiation From Embryonic Stem Cells and iPSCs

50.3 Lung Regeneration


Part VIII: Composite Tissues Allotransplantation

Chapter 51. Current Status of CTA

51.1 Introduction

51.2 Indications and Outcomes

51.3 Immunosuppressive Treatment

51.4 Acute and Chronic Rejections

51.5 Upper Extremity Allotransplantation

51.6 Face Transplantation

51.7 Larynx and Tracheal Transplantations

51.8 Abdominal Wall

51.9 Lower Extremity Transplantation

51.10 Penis Transplantation

51.11 Uterus Transplantation

51.12 Tongue Transplantation

51.13 Conclusions


Chapter 52. Bioengineering of the Lower Urinary Tract

52.1 Bladder Regeneration

52.2 Emerging Rules for Inducing Organ Regeneration

52.3 Ureteral Regeneration

52.4 Urethral Regeneration

52.5 Conclusion


Chapter 53. Upper Airways Regeneration and Bioengineering

53.1 The Upper Respiratory Tract

53.2 Airway Pathologies: The Clinical Need

53.3 Airway Reconstruction: A Challenging Surgical Issue

53.4 Airway Tissue Engineering: A Possible Functional Solution

53.5 Conclusions


Chapter 54. Skin Regeneration and Bioengineering

54.1 Introduction

54.2 Important Technologies

54.3 Future

54.4 Conclusions


Chapter 55. The Use of Skin Substitutes in the Treatment of Burns

55.1 Introduction

55.2 Aim and Method

55.3 Treatment of Burns

55.4 Economic Issues

55.5 Challenges and Future Directions


Chapter 56. Bone Regeneration and Bioengineering

56.1 Bone Engineering in the Last 20 Years

56.2 New Regenerative Medicine Approach to Bone Repair

56.3 The Paradigm Shift: Biomimetic Stimulation of Endogenous Bone Repair and Regeneration

56.4 Learning Nature’s Lesson: Providing Insight into Bone Regeneration

56.5 Biofunctionalizing the Scaffold for Endogenous Bone Repair

56.6 Single versus Multiple Growth Factor Delivery: Providing the Right Signals


Chapter 57. Nerve Regeneration and Bioengineering

57.1 Introduction

57.2 Current Treatment Options and Their Limitations

57.3 Tissue Engineering Strategies

57.4 Conclusion and Future Prospects


Chapter 58. Vessel Regeneration and Bioengineering

58.1 Introduction

58.2 Materials

58.3 Cell Types

58.4 Cell Seeding Technique

58.5 Mechanism of Neotissue Formation in TEVGs

58.6 Clinical Application of TEVGs in Congenital Heart Disease

58.7 Perspectives for the Future


Chapter 59. Corneal Bioengineering

59.1 Stratified Epithelia

59.2 Identification of Human Squamous Epithelial Stem Cells: the Holoclone-Forming Cell

59.3 Structure and Function of Corneal Epithelium

59.4 The Limbal Epithelial Stem Cells

59.5 Culture Method of Limbal Stem Cell for Graftable Epithelium

59.6 Learning Stem Cell Biology from Clinics

59.7 Alternative Methods of Autologous Graft Cultivation on Different Substrates

59.8 Alternative Stem Cell Sources

59.9 GMP and Implications for Regulation

59.10 Concluding Remarks



Chapter 60. Esophagus Bioengineering

60.1 Introduction

60.2 Regenerative Medicine

60.3 Future Perspectives

60.4 Conclusion


Part IX: Immunosuppression-free Transplantation in the Regenerative Medicine Era

Chapter 61. Stem Cell-Based Approach to Immunomodulation

61.1 Immunomodulation

61.2 Hematopoietic Stem Cells

61.3 Mesenchymal Stromal Cells

61.4 Clinical Application of MSCs in Transplantation

61.5 Concluding Remarks



Chapter 62. Immunosuppression-Free Renal Transplantation

62.1 Graft Tolerance: Immunological Background and Definition

62.2 Lessons Learned from Immunology

62.3 Ethical Considerations and Concerns Regarding Transplantation Tolerance-Inducing Regimens

62.4 Clinical Transplantation Tolerance Induction

62.5 Clinical Tolerance Strategies Based on T-Cell Depletion

62.6 Clinical Tolerance Strategies Based on Regulatory Mechanisms

62.7 Immunosuppressive Drugs in the Context of Clinical Organ Tolerance Induction

62.8 Chemokine Receptor-Mediated Trafficking of Tregs

62.9 Obstacles and Perspectives in COT


Chapter 63. Immunosuppression-Free Liver Transplantation

63.1 Introduction

63.1 Definition of Transplantation Tolerance


Chapter 64. Biomarkers of Operational Tolerance in Liver Transplantation

64.1 Introduction

64.2 Potential Biomarkers of Operational Tolerance in LTx

64.3 Novel Biomarkers

64.4 Biomarkers of Fibrosis

64.5 Conclusions



Chapter 65. Biomarkers of Tolerance in Renal Transplantation

65.1 Introduction

65.2 Biomarkers of Chronic Rejection

65.3 Biomarkers of Transplantation Tolerance


Chapter 66. Immunocloaking

66.1 The Immune Response to a Vascularized Allograft

66.2 Potential of Modulating the Immunogenicity of Vascularized Allografts: Concept of Immunocloaking

66.3 Initial Immunocloaking Studies


Chapter 67. The Need for Immune Modulation Despite Regenerative Medicine

67.1 Introduction

67.2 Definitions and Historical Notes

67.3 The Immune Mechanisms That Sustain Self-Tolerance: Central and Peripheral Tolerance

67.4 Strategies to Promote Tolerance Applicable to Regenerative Medicine

67.5 Conclusions



Chapter 68. Stem Cells Approach to I/R Injury

68.1 Candidate Stem Cells for Regenerative Medicine

68.2 Functions of MSCs

68.3 Ischemia/Reperfusion Injury Framework

68.4 Prevention of Solid Organ I/R Injury with MSCs

68.5 Conclusions


Competing Interests


Chapter 69. Xenotransplantation: Past, Present, and Future

69 Xenotransplantation



Chapter 70. Regenerative Medicine as an Industry

70.1 Introduction

70.2 Tissue Engineering and Regenerative Medicine

70.3 The Market of TE, Mechanisms and Perspectives

70.4 A Cultural Dichotomy Between Biomaterials and Cells: Where to Place the Bet?

70.5 Conclusion



Chapter 71. Ethics in Regenerative Medicine and Transplantation

71.1 Introduction

71.2 Blazing the Trail

71.3 Trail Markers

71.4 Making (and Breaking) the Bank

71.5 Summary: Beyond the Trail’s End


Chapter 72. Epilogue: Organ Bioengineering and Regeneration as The New Holy Grail of Organ Transplantation

72.1 Introduction

72.2 Organ Transplantation as a Halfway Technology

72.3 Why Pursuing an IFS?

72.4 Principles of OBR

72.5 OBR as the New Holy Grail for Transplantation




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About the Editor

Giuseppe Orlando

Transplant surgeon scientist, specializing in kidney and pancreas transplantation, as well as in abdominal organ bioengineering and regeneration. My main achievements have been in the field of steroid-free immunosuppression (IS), IS minimization and clinical tolerance after liver transplantation, as well as in the development of platforms for renal, small bowel and endocrine pancreas bioengineering and regeneration research. The main goal of my investigations is to bio-engineer and implant in humans renal organoids, insulin-producing cells and segments of small bowel. The ability to produce kidneys, insulin-producing cells and small bowel from patient’s own cells will revolutionize transplant medicine. The main goal of my scientific production is to orchestrate the transition of organ transplantation towards a regenerative medicine-focused type of research. I originally hail from Rome, Italy, where I grew up, matriculated, attended medical school, and received training in general and transplant surgery. I also participated in fellowships in Paris (Liver Unit, Paul Brousse Hospital, Dir: Henri Bismuth, 6 months) and Brussels (General and Transplant Surgery, Catholic University of Leuven, Dir: Jan Lerut, Jean Bernard Otte, Jean De Ville De Goyet, 31 months). 2006-2008, I was a practicing transplant surgeon at the University of L'Aquila, Italy. 2008-2011, I received and implemented the distinguished Marie Curie International Outgoing Fellowship, for which I spent 2 years at the Wake Forest Institute of Regenerative Medicine (Winston Salem, USA) and 1 year at the Transplant Research Immunology Group (Oxford, UK), specializing in organ bioengineering and regeneration and transplant immunology. I have authored more than 135 research papers, review articles, and book chapters. I have just published – as editor in chief – a book on organ transplantation and regenerative medicine which is destined to set a new standard in transplant and regenerative medicine literature and to become a referral work for the future generations of specialists of both fields. I am a member of numerous transplant societies and am on the board and act as a regular reviewer for a number of relevant journals.

Affiliations and Expertise

Marie Curie Fellow, Assistant Professor of Surgery, Department of General Surgery, Section of Transplantation, Wake Forest Baptist Health Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA


"It is without doubt a very valuable book that captures well the current status of the many areas it addresses...It is a superb summary of the current status of RM and organ transplantation."--Expert Review of Clinical Immunology, Regenerative Medicine Applications in Organ Transplantation

"…represents an invaluable reference for students, physicians, and researchers who are interested in getting a comprehensive, up-to-date snapshot on how regenerative medicine and organ transplantation are reshaping the medical profession."--Transplantation,November 27,2014

"…an invaluable reference for students, physicians, and researchers who are interested in getting a comprehensive up-to-date snapshot on how regenerative medicine and organ transplantation are reshaping the medical profession."--Transplantation, Nov 27 2014

"Given the implications that a chronic shortage of organs has on public health and society, this book is a valuable resource for students and professionals seeking to do something about this problem by taking advantage of cutting-edge developments in one of those most dynamic scientific disciplines existing today, namely regenerative medicine."--Regenerative Medicine 2014 9(3)
"The text is well organized…Chapters on tracheal reconstruction and bladder reconstruction are impressive in demonstrating proximity to clinical utility and indicate that simple structural elements can be manufactured and implanted in humans to bridge a limited defect…if you want to spark your enthusiasm for what is to come, then this textbook is a fine first step into the future."--American Journal of Transplantation, June 2014
"With beautiful illustrations throughout that greatly enhance the overall reading experience of this book, this book is a must-have for anyone interested in tissue engineering and organ transplantation. This is one of the best textbooks I have come across that combines surgery with science, and it is a must for all surgeon-scientists involved in tissue engineering and organ transplantation."--BCS Online, April 3, 2014
"This book succeeds in providing a detailed and comprehensible description of current and future therapies for solid organ replacement. It is unique in that it encompasses all solid organs and compiles a great deal of research. It will serve as a valuable reference for all those involved in the evolution of transplantation." Rating: 4 Stars--Organ Transplantation review on, January 24, 2014