Pancreas and Beta Cell Replacement is the inaugural volume of the Regenerative and Transplant Medicine series. The idea for this new book series spawned from the observation that the regenerative medicine field is progressing at such a fast pace that the way we currently think and practice transplant medicine is rapidly changing, faster than we could ever imagine. This series was therefore conceived to bring together experts from both the transplant and regenerative medicine fields, to share knowledge first, but also to introduce the transplant audience to the remarkable progress that has occurred in regenerative medicine over the past few decades. At the same time, we intend to illustrate to researchers and operators in the regenerative medicine field the numerous platforms that transplant medicine offers for the application of their technologies. To the publisher and the editors of this series and volumes there is no doubt that regenerative medicine will shape and define the future of transplant medicine.
This volume focuses on pancreas and beta cell replacement and illustrates how progress in biomaterial sciences, stem cell biology, gene editing, cell, tissue and organ bioengineering and regeneration, along with advances in xenotransplantation are revolutionizing the field. Written by the world’s experts in the fields of pancreas, islet and xenotransplantation, as well as regenerative medicine, it represents a valuable educational tool for those in the fields of clinical transplantation, researchers in the field of regenerative medicine, transplant medicine, diabetes and immunology, as well as for medical and health science students, those in academia, the biotech industry and regulatory agencies working to advance the field. At the end of the book, it will become clear to the reader that beta cell replacement offers a vast array of platforms for the application of regenerative medicine technologies to transplant medicine.
Author(s): Wayne Hawthorne
Series: Regenerative and Transplant Medicine, 1
Publisher: Academic Press
Year: 2022
Language: English
Pages: 216
City: London
Cover
Title Page
Copyright
Contributors
Pancreas and beta cell replacement: An overview
Introduction
Historical perspectives of whole pancreas transplantation
Into the current era of pancreas transplantation
Current success rates for pancreas transplantation
Historical perspectives of islet cell transplantation
Significant improvements to isolation outcomes
The donor and donor pancreas
Effect of cold ischemic time (CIT)
Organ donor age effects
Surgical retrieval
Effect of organ preservation and transport
Machine perfusion and persufflation
In review
Acknowledgments
References
Whole pancreas transplantation: Advantages and disadvantages, and an overview of new technologies in organ resuscitation
Introduction
Advantages of pancreas transplantation
Diabetic nephropathy
Retinopathy
Peripheral neuropathy/autonomic neuropathy
Macrovascular disease: Peripheral, cardiac, and neurovascular
Disadvantages of pancreas transplantation
Vascular thrombosis
Pancreatic exocrine leakage and re-laparotomy
Peri-pancreatic collections, mycotic aneurysms, and other complications
New technology in pancreas resuscitation
Hypothermic machine perfusion
Normothermic machine perfusion
Conclusion
References
Pancreas resuscitation for whole pancreas transplantation
Introduction
History and current strategies of pancreas preservation for transplantation
Organ preservation solutions (OPS)
Donor assessment
The impact of ischemia and ischemia–reperfusion in the pancreas
Ischemia
Reperfusion and ischemia–reperfusion injury (IRI)
Graft pancreatitis
The steatotic pancreas and IRI
Resuscitation of the pancreas for whole organ transplantation
Two-layer method
Persufflation (PSF)
Machine perfusion (MP)
Hypothermic machine perfusion (HMP)
Normothermic machine perfusion (NMP)
Should there be a strict classification of temperatures in machine preservation?
Can the benefits of machine perfusion improve islet isolation?
The future of perfusion in pancreas transplantation: What needs to happen and what difference will it make?
NMP allows organ assessment
Concluding remarks
References
Normothermic regional perfusion for whole pancreas and islet transplantation
Introduction
Donors after circulatory death
DCD pancreas and islet cell transplant
Normothermic regional perfusion: Methodology
DCD-NRP involving cardiothoracic organs
Organ assessment during normothermic regional perfusion
Mechanistic insights into how normothermic regional perfusion works
Ischaemic preconditioning
Physiological effects of NRP and evidence of reconditioning
Donor selection for DCD-NRP: Transplant organ utilization
Evidence for use of NRP
Liver transplant outcomes from DCD-NRP
Kidney transplant outcomes from DCD-NRP
Pancreas outcomes and future directions for NRP and the pancreas
References
Allogeneic islet isolation: Methods to improve islet cell transplantation with new technologies in organ transplant retriev ...
Introduction
Allogeneic islet transplantation
Clean room facility and equipment
Donor selection
Pancreas procurement
Organ preservation
Human islet isolation procedure
Tissue-dissociation enzyme blends for human islet isolation
Recombinant enzymes for human islet isolation
Enzyme combinations for human islet isolation from young donor pancreases
Cost-effective enzyme combinations for human islet isolation
Purification
Islet release criteria
Future perspectives
Acknowledgments
References
Auto islet isolation: Methods in removal and isolation from fibrosed and autolyzed pancreata
Introduction
Autologous islet transplant
Pancreatitis: Characterized by fibrotic tissue and duct obstruction
Pancreatectomy
Total pancreatectomy with islet autotransplantation (TP-IAT)
Pancreatitis: Importance of prompt surgical treatment
Pancreatitis and inherent challenges to successful autotransplantation
Total pancreatectomy with islet autotransplantation (TP-IAT): Outcomes
Clinical islet transplant facility requirements reduce disease transmission, increase safety, standardize procedures, and m ...
Introduction
Regulation of autologous islets
Islet quality assessment
The vulnerability of islet cells to contamination
Use of a clean room to manufacture islet cells
Specific equipment needs for an auto islet lab
Procedures
Supplies and reagents
Outcome analysis
Auto islet transplantation
Autologous transplant: From patient to processing
Basic surgical procedure to remove pancreas
Total pancreatectomy procedure
Pancreas transfer: UW and HTK solutions
Pancreas transfer: Temperature
Digestion of fibrotic pancreata
Autologous tissue processing: Enzymes and modifications of enzymatic parameters for fibrotic pancreas
Modification of traditional mechanical digestion methods
Improving pancreatic duct patency with calculi removal
Autologous transplant: From processing to patient
Auto islet transport
Surgical transplantation of autologous islets
Transplantation site: Risk vs benefit
Autologous transplant: Factors affecting patient outcomes
Pancreatic islet mass
Tissue volume
Age and disease duration
Postoperative complications
Quality of life after autologous transplant
References
Oxygenation of the pancreas
Introduction
Pancreas transplantation
Specific challenges in pancreas preservation for islet transplantation
Hypoxia in islets: Structural, biochemical, and molecular considerations
Fundamental concepts of organ oxygenation
Commonly used and alternative pancreas preservation methods to improve oxygenation
Static cold storage is the most commonly used clinical pancreas preservation method
Alternative preservation methods to improve oxygenation of the pancreas
Two-layer method
Machine perfusion
Hypothermic
Normothermic
Oxygen persufflation
Conclusion
References
Encapsulation devices to enhance graft survival: The latest in the development of micro and macro encapsulation devices to ...
Introduction
Design of reactors and transplantation devices
Microencapsulation
Macroencapsulation
Biocompatibility
Site of implantation
Immune protection of encapsulated transplants
Allograft protection
Xenograft protection
Autoimmune protection
Device vascularisation
Efficacy
Conclusion
References
Transgenic pigs for islet xenotransplantation
Introduction
Protecting porcine islet xenografts from the innate immune response
Removing the carbohydrate targets of pre-formed xenoantibodies
Inhibiting the activation of complement by expressing human complement regulatory proteins (hCRPs)
The GTKO/hCRP combination
Inhibiting coagulation and thrombosis
Other strategies to control inflammation and innate immune cell activity
Protecting porcine islet xenografts from adaptive immunity
Local immunosuppression by secretion of immunomodulatory molecules
Downregulation or modification of SLA class I and II
Expression of T cell inhibitory and apoptotic signals
Improving the compatibility and function of porcine islets
Reducing infectious risk
The next generation of highly modified donor pigs
Which transgenes are relevant for alternative transplant sites and modalities?
Can genetic modification to protect islet xenografts have a detrimental impact on islet function?
Summary
References
Xenogeneic pancreatic islet cell transplantation—Application of pig cells and techniques for clinical islet cell xenotransp ...
Introduction
Porcine islets as an alternative source for beta cell replacement
Sources of porcine xenoislets
Embryonic and fetal tissues
Neonatal tissues
Young adult and adult tissues
Hurdles to successful transplantation
Instant blood-mediated inflammatory reaction
Acute cell-mediated rejection
Acute antibody-mediated rejection
Chronic rejection
Techniques to control IBMIR and immunological rejection
Genetic modification of the source pig
Encapsulation and new techniques for protecting islets
Control of IBMIR
Control of immunological rejection
Clinical application of xenoislet cell transplantation
DPF pigs
Regulation
Strategies for the successful transplantation
Combination of proper techniques
Future perspectives
Acknowledgment
References
The development of stem cell therapies to treat diabetes utilizing the latest science and medicine have to offer
Introduction to stem cells—What they are and how they can help treat disease
Embryonic stem cells (ESCs)
In vitro differentiation of hESCs
Human-induced pluripotent stem cells
Pancreatic embryological structure and cell signaling
Pancreatic beta-cells physiology in relation to stem cells
Stem cell differentiation strategies—An overview of the past two decades
Strategies behind developing a pancreatic differentiation protocol
State of the art for the pancreatic differentiation
Final considerations
References
Regeneratively speaking: Reflections on organ transplantation and beta cell replacement in the regenerative medici
A historical perspective
Organ transplantation: A halfway technology
Regenerative medicine technologies
Decellularization
General concepts
Beta cell replacement
3D printing
General concepts
Beta cell replacement
Stem cell technologies
General concepts
Beta cell replacement
Organoids
General concepts
Beta cell replacement
Chip technology
General concepts
Beta cell replacement
Final remarks
References
Index
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D
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