Organ Repair and Regeneration

Preserving Organs in the Regenerative Medicine Era

1st Edition - January 14, 2021
Editors: Giuseppe Orlando, Shaf Keshavjee
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 1 9 4 5 1 - 5
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 1 9 4 5 2 - 2

Organ Repair and Regeneration: Preserving Organs in the Regenerative Medicine Era encompasses updates on all organs, from the kidneys, to the lungs, liver, pancreas, intest… Read more

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Organ Repair and Regeneration: Preserving Organs in the Regenerative Medicine Era encompasses updates on all organs, from the kidneys, to the lungs, liver, pancreas, intestines, and beyond. Chapters cover the pathophysiology of ischemia-reperfusion, repairing organs with MSC, repairing cardiac allografts in situ, and much more. The book conceptualizes the idea that the modern approach to organ preservation is ante literam, a form of organ repair and regeneration which, per se, is referred to as a field of health sciences under the umbrella of regenerative medicine. This book demonstrates the merging of regenerative medicine and organ transplantation.

Cover image
Title page
Table of Contents
Copyright
Contributors
Foreword
Preface
Chapter 1. Ischemia-reperfusion injury
Concepts and molecular mechanisms of ischemia reperfusion injury
Ischemia-reperfusion injury in acute kidney injury and transplantation
Future directions
Chapter 2. Machine perfusion for donor organ repair: from vision to everyday clinical practice
Strategies for donor pool expansion
Machine perfusion and liver anatomy
Mechanisms of preservation injury and graft protection
Graft viability assessment
Clinical practices of ex situ machine perfusion
Chapter 3. Assessing and reconditioning kidneys using normothermic machine perfusion
Introduction
Development of NMP for renal grafts
Perfusion solutions
Clinical normothermic machine perfusion
Quality assessment and conditioning
Repair mechanisms and potential for reconditioning
Future developments
Conclusion
Chapter 4. Autologous cells for renal allograft repair
Introduction
Cell therapy in solid organ transplantation
The rationale and potential advantages for the use of autologous cells for transplant organ regenerative therapy
Candidate cell types for regenerative peri-transplant therapy
Sources of autologous regenerative cells
Cellular makeup, properties, and mechanisms of action of adipose-derived regenerative cells
Review of literature on the effect of systemic/organ dysfunction on fat SVR cellular composition and efficacy
Bedside production of ADRCs
Efficacy of ADRC's in preventing IRI/promoting tissue regeneration in kidney and other organ systems
Adipose-derived regenerative cell model of renal regenerative therapy
Mechanism of ADRC action in promoting renal allograft repair
Synergistic repair with novel ex vivo perfusion technologies
Chapter 5. Repairing organs with MSC
Stem cell–mediated regeneration of damaged renal allografts: the hope and the reality
Inherent regenerative potential and limitations
The role of the immune system in regeneration
Association of delayed graft function with chronic rejection
Stem cells
Source of stem cells
The role of prolonged ex vivo perfusion platforms for tissue engineering
Evidence supporting the potential to regenerate renal allografts
HREC
Potential of MSC-mediated renal regeneration
Optimal source of MSC
MSC-derived products
MSC clinical trials
Renal regeneration during ex vivo warm perfusion
Chapter 6. Resuscitation of the pancreas: whole organ and islet cell technologies into the machine era
Abbreviations
Pancreas and islet cell transplantation—the need, current indications, and organ acceptance criteria
Current methods of static preservation of the pancreas
Defining the “marginal” pancreas
Utilization and outcomes of pancreas and islet cell transplantation from marginal or expanded criteria donors
Resuscitation and regeneration of the whole pancreas before transplantation
Resuscitation and regeneration of the pancreas before islet cell transplantation
Concluding remarks
Chapter 7. Assessment of extended criteria liver grafts during machine perfusion. How far can we go?
Background
Liver function
Animal models
Clinical studies
Regional perfusion
Future considerations
Chapter 8. RNA interference in organ transplantation: next-generation medicine?
Abbreviations
Introduction
Gene silencing with RNA interference
RNAi in organ transplantation
Conclusions
Chapter 9. Repairing cardiac allografts on ex situ perfusion devices
Introduction
Current state of heart transplantation
MP and heart transplantation
Standard criteria brain-dead donors
Marginal criteria brain-dead donors
Donation after circulatory death donors
Future directions
Conclusions
Chapter 10. Repairing cardiac allografts in situ
What is organ repair?
How does the donor heart gets damaged?
Why fuss about donor heart repair?
Utilization of organs and the emerging resource of DCD hearts
Donation after circulatory determined death
In situ reanimation of cardiac allografts
How do we assess function in DCD hearts?
So, is it worth the effort? Outcomes of DCD heart transplants
How to improve? The importance of time
So where next? Future directions
Chapter 11. Steatotic livers for transplantation: improving utilization of a prevalent resource through organ repair
Introduction
Limitations of steatotic grafts for liver transplantation
Historic uses of steatotic livers for transplant
Current use of machine perfusion for steatotic livers
Future therapies for repairing steatotic livers
Conclusion
Chapter 12. Implementing the vision: the organ repair center
Chapter 13. Mitochondria transplantation in organ damage and repair
Introduction
Technical considerations
Conclusion
Chapter 14. How the transplant landscape is changing in the regenerative medicine era
Abbreviations
A historical perspective
Organ transplantation: a halfway technology
Pursuit of immunosuppression-free transplantation
RM applications in current organ transplantation
Developing regenerative medicine technologies
What the immediate future holds
Index

Giuseppe Orlando

Giuseppe Orlando, MD, PhD, Marie Curie Fellow, is an Associate Professor and a kidney and pancreas transplant surgeon scientist at the Wake Forest University School of Medicine, in Winston Salem, USA. His research aims at developing platforms for the bioengineering and regeneration of transplantable organs, and at developing therapies to enhance the innate ability of the human body to repair itself after damage. His literature output aims at bridging organ transplantation to regenerative medicine.

Affiliations and expertise

Section of Transplantation, Wake Forest University Baptist Medical Center Medical Center Boulevard Winston-Salem, NC, USA

Shaf Keshavjee

Dr. Shaf Keshavjee completed his medical training at the University of Toronto in 1985, and subsequently trained in General Surgery, Cardiac Surgery and Thoracic Surgery at the University of Toronto followed by fellowship training at Harvard University and the University of London for airway surgery and heart-lung transplantation, respectively. He currently leads a team whose studies in transplantation will have a significant impact on treatment outcomes for patients with lung disease at UHN and around the world. Dr. Keshavjee was appointed UHN’s Surgeon-in-Chief in 2010. An integral part of the Division of Thoracic Surgery at UHN, Dr. Keshavjee has taken on leadership roles in all facets of this specialized area of care: as a skilled surgeon and Director of the Toronto Lung Transplant Program; and as a researcher and Director of the Latner Thoracic Surgery Research Laboratories. To improve lung function after transplantation, Dr. Keshavjee has developed a lung preservation solution to preserve donor lungs en route to transplant. This solution has become the standard technique used by transplantation programs around the world. Dr.Keshavjee has further attracted worldwide attention for his pioneering research to recondition and repair injured human donor lungs using a combination the Toronto XVIVO Lung Perfusion System, making them suitable for transplantation into patients and enhancing the number of donor lungs that are available. Dr. Keshavjee has served on the Board of Directors of the International Society for Heart and Lung Transplantation, The Canadian Society of Transplantation and on the Governing Council of the American Association for Thoracic Surgery. He has received numerous awards for his continuing contributions to his field, including the George Armstrong Peters Young Investigator Award, Canada’s Top 40 Under 40Award, the Colin Woolf Award for Excellence in Continuing Medical Education and the highest award for research achievement in the Department of Surgery: the Lister Prize in Surgery.Dr. Shaf Keshavjee completed his medical training at the University of Toronto in 1985, and subsequently trained in General Surgery, Cardiac Surgery and Thoracic Surgery at the University of Toronto followed by fellowship training at Harvard University and the University of London for airway surgery and heart-lung transplantation, respectively. He currently leads a team whose studies in transplantation will have a significant impact on treatment outcomes for patients with lung disease at UHN and around the world. Dr. Keshavjee was appointed UHN’s Surgeon-in-Chief in 2010. An integral part of the Division of Thoracic Surgery at UHN, Dr. Keshavjee has taken on leadership roles in all facets of this specialized area of care: as a skilled surgeon and Director of the Toronto Lung Transplant Program; and as a researcher and Director of the Latner Thoracic Surgery Research Laboratories. To improve lung function after transplantation, Dr. Keshavjee has developed a lung preservation solution to preserve donor lungs en route to transplant. This solution has become the standard technique used by transplantation programs around the world. Dr.Keshavjee has further attracted worldwide attention for his pioneering research to recondition and repair injured human donor lungs using a combination the Toronto XVIVO Lung Perfusion System, making them suitable for transplantation into patients and enhancing the number of donor lungs that are available. Dr. Keshavjee has served on the Board of Directors of the International Society for Heart and Lung Transplantation, The Canadian Society of Transplantation and on the Governing Council of the American Association for Thoracic Surgery. He has received numerous awards for his continuing contributions to his field, including the George Armstrong Peters Young Investigator Award, Canada’s Top 40 Under 40Award, the Colin Woolf Award for Excellence in Continuing Medical Education and the highest award for research achievement in the Department of Surgery: the Lister Prize in Surgery.

Affiliations and expertise

Faculty of Medicine, University of Toronto, Toronto, ON Canada

Life Sciences

Physical Sciences & Engineering

Social Sciences & Humanities

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