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Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas: Volume 2 [Kõva köide]

Edited by , Edited by (IRCCS Ospedale San Raffaele, Director of Diabetes Research Institute and Director of Human Islet Transplantati), Edited by , Edited by (Section of Transplantation, Wake Forest University Baptist Medical Center Medical Center Boulevard Winston-Salem, NC, USA), Edited by
  • Formaat: Hardback, 560 pages, kõrgus x laius: 276x216 mm, kaal: 1680 g
  • Ilmumisaeg: 08-Nov-2019
  • Kirjastus: Academic Press Inc
  • ISBN-10: 0128148314
  • ISBN-13: 9780128148310
Teised raamatud teemal:
  • Formaat: Hardback, 560 pages, kõrgus x laius: 276x216 mm, kaal: 1680 g
  • Ilmumisaeg: 08-Nov-2019
  • Kirjastus: Academic Press Inc
  • ISBN-10: 0128148314
  • ISBN-13: 9780128148310
Teised raamatud teemal:

Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas, Volume 2, sets a new standard in transplant and regenerative medicine. The book details the state-of-the-art in modern islet auto-transplantation, also discussing current progress in regenerative medicine research in diabetes medicine. Regenerative medicine is changing the premise of solid organ transplantation, hence this volume catalogs technologies being developed and methods being implemented. Bioengineering and regenerating beta cells, clinical pancreas and islet transplantation, tissue engineering, biomaterial sciences, stem cell biology and developmental biology are all addressed and applied directly to diabetes medicine.

  • Provides comprehensive and cutting-edge knowledge of whole pancreas and islet transplantation
  • Addresses imaging, treatment, scaffold technology, the use of stem cells to generate insulin, 3D printing, and more
  • Offers an update on the progress of regenerative medicine research aimed at beta cell replacement for the treatment of diabetes
Contributors xi
A Islet auto-transplantation
Section I Chronic pancreatitis
1 Etiopathogenesis and pathophysiology of chronic pancreatitis
Jagan Kalivarathan
Kunal Yadav
Will Bataller
Nathaniel W. Brigle
Mazhar A. Kanak
Etiopathogenesis
7(1)
Alcohol-induced chronic pancreatitis
7(2)
Autoimmune pancreatitis
9(1)
Genetic pancreatitis
10(2)
Hereditary pancreatitis
12(1)
Recurrent acute pancreatitis
13(1)
Ductal obstruction
13(1)
Pancreas divisum
14(1)
Sphincter of Oddi dysfunction
14(1)
Pancreatic trauma
15(1)
Tropical chronic pancreatitis
16(1)
Drug toxicity-induced pancreatitis
16(1)
Idiopathic
17(1)
Gallbladder dysfunction
17(1)
Smoking and pancreatitis
18(1)
Pathophysiology
18(1)
Exocrine insufficiency
19(1)
Endocrine insufficiency and diabetes mellitus
19(1)
Pathophysiology of pain
20(1)
Calcification
21(1)
Fatty infiltration
22(1)
Fibrosis
22(1)
Pseudocysts
22(1)
Atrophy
23(1)
Pancreatic cancer
23(1)
Molecular mechanisms in the development of pancreatitis
24(1)
Conclusion
24(1)
References
25(8)
2 Nonreplacement treatment of chronic pancreatitis: Conservative, endoscopic, and surgical (resection and drainage procedures)
Elizabeth C. Poli
Christopher G. Chapman
Jeffrey B. Matthews
Introduction
33(1)
Clinical evaluation
33(3)
Medical and conservative management
36(1)
Endoscopic and surgical management of chronic pancreatitis
37(9)
Conclusion
46(1)
References
46(5)
Section II Islet auto-transplantation for chronic pancreatitis
3 Requirements for clinical islet laboratories
L. Rodriguez Rilo
Renee Cercone
Jonathan R.T. Lakey
Introduction
51(1)
Allogeneic vs autologous islet
52(1)
Registration with the FDA
53(3)
Registration with other regulatory agencies
56(1)
General requirements for a clinical auto islet lab
56(1)
Facilities and environmental control
56(3)
Equipment
59(2)
Personnel
61(1)
Procedures
62(2)
Inspections
64(1)
References
64(3)
4 Islet isolation for autotransplantation, following total or near total pancreatectomy
Elina Linetsky
Camillo Ricordi
Introduction
67(1)
Islet isolation
68(16)
Conclusions
84(1)
References
85(2)
Further reading
87(2)
5 Strategies to improve islet yield from chronic pancreatitis pancreases intended for islet allotransplantation
Michael A. Goedde
Gopalakrishnan Loganathan
Siddharth Narayanan
Abid Hussain
Christopher M. Jones
Michael G. Hughes
Appakalai N. Balamurugan
Introduction
89(1)
Islet cell isolation
90(1)
Pancreatectomy and pancreas transport
91(1)
Trimming and cannulation of the pancreas
91(1)
Enzyme selection and perfusion
92(1)
Tissue digestion
93(1)
Tissue recombination
94(1)
Purification process
95(1)
Transplant preparation
96(1)
Conclusion
97(1)
Conflict of interest
98(1)
Acknowledgments
98(1)
References
98(3)
6 Surgical techniques for total pancreatectomy and islet autotransplantation
Kaylene Barrera
Sidharth Sharma
Alexander Schwartzman
Rainer W.G. Gruessner
Introduction
101(1)
Indications and contraindications
102(2)
Operative technique
104(7)
Percutaneous infusion/transplantation of islets
111(1)
Postoperative care
111(1)
Complications
112(1)
Outcomes
113(1)
Salvage pancreatectomy
113(1)
Pediatric population
113(1)
Remote processing
113(1)
QOL after TPIAT
113(1)
Future
114(1)
Conclusions
114(1)
Acknowledgments
114(1)
References
114(3)
7 Total pancreatectomy with islet autotransplantation in children
Melena D. Bellin
Sarah J. Schwarzenberg
Matthew Armfield
Srinath Chinnakotla
Introduction
117(1)
Pancreatitis in children
117(2)
Determining when TPIAT is indicated for the management of children with pancreatitis
119(1)
Surgical procedure and islet isolation and transplant in children
119(1)
Postoperative management of the child after TPIAT
120(2)
Short-term and long-term outcomes after TPIAT in children
122(2)
Conclusions
124(1)
References
124(3)
8 Islet autotransplantation: Indication beyond chronic pancreatitis
Lorenzo Piemonti
Rita Nano
Raffaella Melzi
Alessia Mercalli
Davide Socci
Massimo Falconi
Gianpaolo Balzano
Introduction
127(1)
Incidence of pancreatogenic diabetes after pancreatic resection
128(1)
Autologous islet transplantation to prevent or minimize pancreatogenic diabetes in patients requiring total pancreatectomy for chronic pancreatitis
129(1)
Expanding indications for IAT: Nonneoplastic diseases beyond chronic pancreatitis
129(2)
Expanding indications for IAT: Neoplastic benign diseases
131(1)
Expanding indications for IAT: Neoplastic malignant diseases
132(1)
Expanding indications for IAT: Milan protocol
132(1)
Conclusion
133(1)
References
134(7)
Section III Outcomes
9 Postoperative care and prevention and treatment of complications following total pancreatectomy with islet cell autotransplantation
Kristin P. Colling
Ty B. Dunn
Greg J. Beilman
Introduction
141(1)
Patient selection and preoperative preparation
142(1)
Postoperative management and complications
142(4)
Conclusion
146(1)
References
147(2)
10 Metabolic outcomes after total pancreatectomy followed by islet autotransplantation (TPIAT): Mixed blessings
R. Paul Robertson
History and rationale for TPIAT: Points of view
149(1)
Favorable metabolic outcomes: Normal levels of glycemia, HbA1c, and β-cell function
150(1)
Unfavorable metabolic outcomes: Hypoglycemia following meals and exercise and deficient a-cell counter-regulatory response
151(4)
The need to consider nonhepatic transplantation sites
155(1)
References
155(2)
11 Long-term results of TPIAT
Kendall Mceachron
Alexandria Coughlan
Marie Cook
Louise Berry
Greg J. Beilman
Melena D. Bellin
Introduction
157(1)
Surgical outcomes
158(1)
Gastrointestinal function outcomes
159(2)
Pain and quality of life outcomes
161(1)
Metabolic outcomes
162(1)
Survival and cost of care
163(2)
Conclusions
165(1)
References
165(6)
B Bioengineering and regeneration of the endocrine pancreas
Section I Pancreas development and regeneration
12 Embryonic development of the endocrine pancreas
Spencer R. Andrei
Maureen Gannon
Introduction to pancreas development
171(1)
Pancreas development
172(5)
Postnatal islet development and function
177(2)
Conclusions
179(1)
Acknowledgments
180(1)
References
180(3)
13 Human pancreatic progenitors
Mirza Muhammad Fahd Qadir
Giacomo Lanzoni
Camillo Ricordi
Juan Dominguez-Bendala
Introduction
183(1)
Induction and patterning of pancreatic endoderm
184(4)
Lineage specification, proliferation, and compartmentalization of pancreatic progenitors
188(3)
Adult pancreatic progenitors
191(1)
Transdifferentiation in the pancreas
192(1)
Extrapancreatic sources of pancreatic precursors
192(1)
Mesenchymal stem cells as potential sources for pancreatic endocrine cells
193(2)
Therapeutic modulation of pancreatic regeneration and P-cell mass
195(1)
Concluding remarks
195(1)
Acknowledgments
195(1)
References
196(5)
14 Strategies to promote beta-cell replication and regeneration
Xiangwei Xiao
Introduction
201(1)
Beta-cell replication is the major contributor to the postnatal beta-cell growth
202(2)
Cell-cell communications regulate beta-cell proliferation
204(2)
Molecular signaling pathways that control beta-cell proliferation
206(2)
Concluding remarks
208(1)
References
208(7)
15 Diet as a therapeutic approach to diabetes management and pancreas regeneration
Valentina Villani
Laura Perin
Introduction
215(1)
Proper nutrition is key to the maintenance of P-cell homeostasis and function
216(2)
Dietary intervention for T1D: Feasibility, outcome, and recent progress
218(2)
Diet in T2D; The two sides of diet and eating habits as causing factor and potential treatment for T2D
220(1)
Dietary recommendations for women with gestational diabetes
221(1)
Clinical relevance of fasting or fasting-like regimens as a nutritional therapeutic approach in diabetes
222(1)
Molecular mechanisms supporting the potential of fasting and FMD to promote pancreas functional restoration
223(2)
Conclusion
225(1)
References
225(4)
16 The benefits of metabolic/bariatric surgery on diabetes mellitus
Henry Buchwald
Jane N. Buchwald
Introduction
229(1)
History of metabolic/bariatric surgery
230(3)
Metabolic/bariatric surgery for diabetes
233(2)
Nonbariatric metabolic surgery for diabetes
235(1)
Metabolic/bariatric surgery mechanisms
235(2)
The present
237(1)
The future
238(1)
Conflict of interest
238(1)
References
238(5)
Section II Scaffolds for endocrine pancreas bioengineering
17 ECM-based scaffolds for pancreas bioengineering
Ipsita Banerjee
Introduction
243(1)
Extracellular matrix
244(1)
Extracellular matrix in pancreatic islets
244(2)
Tissue engineered islet scaffold incorporating ECM
246(1)
Whole organ engineering of pancreas
246(5)
Hybrid organs using repurposed biological scaffolds: Liver and kidney to pancreas
251(1)
Conclusion
251(1)
References
252(5)
18 Plasma scaffolds for islet transplantation
Elisa Maillard
Introduction
257(1)
Islet microenvironment
257(1)
Integrins and mechanotransduction
258(1)
Concept of anoikis
259(1)
Organoid organization protects islet from anoikis
259(1)
Strategies to counteract anoikis
259(2)
Using plasma as a scaffold
261(2)
Plasma scaffolds for islets: Drawbacks
263(2)
Uses of plasma for other applications
265(1)
Conclusion
265(1)
Acknowledgements
265(1)
Conflict of interest statement
265(1)
References
265(4)
19 A biologic resorbable scaffold for tissue engineering of the endocrine pancreas: Clinical experience of islet transplantation on the omentum
David A. Baidal
Marco Infante
Virginia Fuenmayor
Ana M. Alvarez
Nathalia Padilla
Dora M. Berman
Antonello Pileggi
Elina Linetsky
Gaetano Ciancio
Camillo Ricordi
Rodolfo Alejandro
Introduction: The intrahepatic site for islet transplantation
269(1)
Extrahepatic sites for islet transplantation
270(1)
The greater omentum: A novel site for islet transplantation
270(5)
Conclusions
275(1)
References
275(2)
20 Endothelialized collagen modules for islet tissue engineering
Alexander E. Vlahos
Michael V. Sefton
Introduction
277(1)
Transplantation into the omental pouch of immune competent rats
278(2)
Subcutaneous transplantation into immune-compromised SCID/bg mice
280(4)
Future directions
284(1)
References
285(6)
Section III Islet encapsulation
21 Conformal coating
Aaron A. Stock
Alice A. Tomei
Introduction
291(3)
Conformal coating technology
294(12)
Conclusion and future directions
306(1)
Disclosure
306(1)
References
306(1)
22 Co-encapsulation of ECM proteins to enhance pancreatic islet cell function
Amanda Child
Emily J. Larkin
Magali J. Fontaine
Introduction
307(1)
Overview of the islet extracellular matrix
308(1)
Effects of ECM co-encapsulation on P-cell survival
309(1)
Effects of ECM co-encapsulation on P-cell function
310(1)
Effects of ECM co-encapsulation on p-cell proliferation
311(1)
Future directions
311(1)
References
312(3)
23 Co-encapsulation of mesenchymal stromal cells to enhance islet function
Vijayaganapathy Vaithilingam
Bernard E. Tuch
Type 1 diabetes and islet transplantation
315(1)
Current issues with encapsulated islet transplantation
316(1)
Mesenchymal stromal cells
317(1)
MSC and islet transplantation
318(1)
Islets and MSC co-encapsulation
319(5)
Conclusion
324(1)
References
324(5)
24 Silk-based encapsulation materials to enhance pancreatic cell functions
Manishekhar Kumar
G. Janani
Magali J. Fontaine
David L. Kaplan
Biman B. Mandal
Introduction
329(1)
Silk as a biomaterial
330(2)
Silk matrices used for islet culture and encapsulation
332(4)
Conclusions and future perspectives
336(1)
Acknowledgments
336(1)
References
336(3)
25 Cell pouch devices
Amish Asthana
Sean Muir
Deborah Chaimov
Giuseppe Orlando
Introduction
339(1)
Cell encapsulation technology
340(1)
Macroencapsulation devices
340(2)
Concluding remarks
342(1)
References
342(5)
Section IV Stem cells to generate insulin producing cells
26 Pancreas progenitors
Guido Carpino
Vincenzo Cardinale
Eugenio Gauido
Domenico Alvaro
Introduction
347(1)
Regeneration of pancreatic islets
348(2)
Biliary tree stem/progenitor cells and the network of hepatic, biliary, and pancreatic stem/progenitor cell niches
350(2)
Pancreatic progenitor cells
352(1)
Pancreatic duct gland as the niche of pancreatic progenitors
353(2)
Conclusions
355(1)
References
355(4)
27 Human embryonic stem cells (hESC) as a source of insulin-producing cells
Sara Dutton Sackett
Daniel M. Tremmel
Austin K. Feeney
Samantha A. Mitchell
Jon S. Odorico
Introduction
359(2)
Current therapeutic approaches and challenges
361(1)
Pancreas development
362(1)
Stem cell-derived p cells
363(4)
Hurdles still preventing a final functional product
367(3)
Immunogenicity
370(2)
Current clinical trials of stem cells for diabetes
372(1)
Interspecies organogenesis and stem cells
373(1)
Conclusion
374(1)
References
374(7)
28 Human-induced pluripotent stem cells (iPSC) as a source of insulin-producing cells
Silvia Pellegrini
Valeria Sordi
Pluripotent stem cells: Embryonic stem cells and somatic cell nuclear transfer
381(1)
Every cell can be pluripotent: The discovery of induced pluripotent stem cells
382(1)
iPSC are in the clinic: active protocols in humans
383(1)
iPSC for β-cell replacement: In vitro differentiation into β-cells
384(4)
Immunogenicity of iPSC-derived cells
388(1)
Graft protection
389(2)
Safety of iPSC-derived cells
391(1)
Conclusions
392(1)
References
392(5)
29 Ductal cell reprograming to insulin-producing cells as a potential beta cell replacement source for islet auto-transplant recipients
Siddharth Narayanan
Gopalakrishnan Loganathan
Abid Hussain
Stuart K. Williams
Appakalai N. Balamurugan
Introduction
397(2)
Ductal cells as a potential source for beta cell regeneration
399(1)
In vitro reprogramming of pancreatic ductal cells
399(2)
In vivo studies on the pancreatic ductal progenitor cells
401(1)
Controversies regarding endocrine differentiation from ductal lineages
401(1)
Conclusions and future perspectives
402(1)
Conflict of interest
403(1)
Acknowledgments
403(1)
References
403(4)
30 Synthetic biology technologies for beta cell generation
Pratik Saxena
Daniel Bojar
Henryk Zulewski
Martin Fussenegger
Introduction
407(3)
Synthetic biology approaches for generating beta cells
410(4)
Artificial designer cells
414(2)
Synthetic biology---Moving toward clinical applications
416(1)
References
417(6)
Section V Animal-based platforms for pancreas bioengineering
31 Xenotransplantation of the endocrine pancreas
Benjamin Smood
Rita Bottino
David K.C. Cooper
Introduction
423(1)
A brief history of xenotransplantation
424(2)
Optimizing the pig-to-NHP model
426(1)
Laying the foundation: preclinical studies in islet xenotransplantation
427(9)
Justification for translation to clinical trials
436(2)
Future directions
438(1)
Conclusions
439(1)
Acknowledgment
439(1)
Conflict of interest
439(1)
References
439(8)
32 Interspecies blastocyst complementation
Benjamin S. Freedman
Introduction
447(1)
Basic principles of IBC
448(1)
Generation of pancreas with IBC
448(1)
Transplantability of IBC pancreas
449(1)
Advantages of IBC
449(1)
Pretransplant immunogenicity
450(1)
Posttransplant immunogenicity
451(1)
Potential for IBC vasculature
451(1)
Autograft tolerance
452(1)
Allograft considerations
452(1)
Efficiency of IBC
453(1)
Breeding schemes
453(1)
Gene editing with IBC
454(1)
Suitability of large animal hosts
455(1)
Ethical concerns
455(1)
Outlook
456(1)
References
456(5)
Section VI Tissue engineering technologies applied to (J-cell replacement
33 Bioengineering, biomaterials, and |3-cell replacement therapy
Rick De Vries
Adam Stell
Sami Mohammed
Carolin Hermanns
Adela Helvia Martinez
Marlon Jetten
Aart Van Apeldoorn
Introduction
461(1)
Immunoprotective barrier strategy
462(1)
Revascularization strategy
463(1)
Biomaterials
464(7)
Islet delivery device fabrication techniques
471(4)
3D Printing in regenerative medicine
475(2)
Future outlook
477(3)
References
480(6)
Further reading
486(1)
34 Subcutaneous islet transplantation using tissue-engineered sheets
Shinichiro Ono
Tomohiko Adachi
Masataka Hirabaru
Hajime Matsushima
Hajimeimamura
Masaaki Hidaka Kojinatsuda
Toshiyuki Adachi
Manpeiyamashita
Mitsuhisa Takatsuki
Tatsuya Kin
Susumu Eguchi
Introduction
487(1)
Subcutaneous islet transplantation
488(1)
Cell sheet engineering in cell transplantation
488(2)
Subcutaneous islet transplantation using cell sheet engineering
490(1)
Our concept of subcutaneous islet transplantation using cell sheet engineering
490(1)
Cell sources
491(1)
Cytokines
491(1)
Previous study
492(1)
Conclusions
492(1)
Conflict of interest
493(1)
References
493(6)
Section VII Regulation and funding
35 Regulation for regenerative medicine-based therapies
Giovanni Migliaccio
Regulatory approach to regenerative medicine in the EU
499(1)
Differences between United States and European Union regulatory framework
500(1)
Therapeutic use of pancreatic cells
501(1)
Conclusion
502(1)
References
502(3)
36 Catalyzing beta-cell replacement research to achieve insulin independence in type 1 diabetes: Goals and priorities
Esther Latres
JDRF mission
505(1)
Beta-cell replacement
506(8)
Additional considerations
514(1)
Conclusion
515(1)
Acknowledgments
515(1)
References
515(2)
Further reading
517(3)
37 Regenerative medicine technologies applied to beta cell replacement: The industry perspective
William Rust
Can a "replenishable" (stem cell-derived) beta cell therapy mimic islet transplant therapy?
520(1)
Immune suppression
521(1)
Beta cells within devices
521(2)
Can the therapy be removed and replaced?
523(1)
Can the therapy be mass-produced?
523(1)
Regulatory approval
523(1)
Cost and reimbursement
524(1)
Patient acceptance
524(1)
Conclusion
524(1)
References
524(2)
Further reading
526(1)
38 Pancreas whole organ engineering
Catalina Pineda Molina
Yoojin C. Lee
Stephen F. Badylak
Introduction
527(1)
Fundamental concepts of tissue development
527(1)
Three-dimensional bioscaffolds for whole organ pancreas engineering
528(7)
Challenges to current approaches
535(1)
References
535(2)
Index 537
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. At the San Raffaele Scientific Institute (Milan, Italy) Lorenzo Piemonti serves as Director of Diabetes Research Institute and Director of Human Islet Transplantation Program. He also serves as Head of the Beta Cell Biology Unit (Diabetes Research Institute), Director of Human Islet Processing Facility, and coordinator of European Consortium for Islet Transplantation that has been providing Human beta Cell Products for research across state barriers in Europe since 2000. He also serves as Professor in Endocrinology at University Vita Salute San Raffaele” of Milan and as Honorary Visiting Professor at Vrije Universiteit of Brussel. His area of expertise is mainly focused on diabetes and pancreatology. In particular he has large experience about diabetes and pancreatic cancer. He had in the past studied the role of innate immunity in islet cell biology (especially in the human model of islet transplantation in type 1 diabetes recipient) and in pancreatic cancer biology (especially the role of chemokines and chemokine receptor system in inducing leukocytes infiltration). More recently, his research interests includes beta cell replacement, immune tolerance induction strategies, dendritic cell biology, stem cells. He currently serves as section Editor of Cell Transplantation-the Regenerative Medicine Journal and of Current Diabetes Reports, as editorial board of Acta Dibetologia, as Councilor of the International Pancreas and Islet Transplantation Association (IPITA) of The Transplantation Society (TTS), as member of the National Committee for Food Safety (2018-2021, Italian Ministry of Health) and previously (2011-2017) as member of the European Pancreas and Islet Transplantation Association (EPITA) committee of European Society for Organ Transplantation (ESOT). Lorenzo Piemonti authored more than 200 original articles published in peer-reviewed journals surveyed in PubMed. h-index (December 2018): 43 Web of Science; 47 Scopus; 53 Google Scholar. Considering the period 2001-2018 Lorenzo Piemonti authored a total of 165 original articles published in peer-reviewed journals for an impact factor of 918.344 (mean impact factor: 5.566) Camillo Ricordi holds the Stacy Joy Goodman Chair in Diabetes Research. He is Professor of Surgery, Distinguished Professor of Medicine, Professor of Biomedical Engineering, Microbiology and Immunology and Director of the Diabetes Research Institute (www.diabetesresearch.org ) and the Cell Transplant Program at the University of Miami. After developing the method for human pancreatic islet isolation, he led the team that performed the first series of successful clinical islet allotransplants to reverse diabetes. He is currently serving as Chairperson of the NIH funded Clinical Islet Transplantation (CIT) Consortium, which standardized cell manufacturing protocols in North America and Europe and just completed the first multicenter FDA Phase III trial of islet transplantation in the US. He is currently Editor-in-Chief of CellR4 (www.cellr4.org) and serves as Founding Chairman of The Cure Alliance (www.thecurealliance.org) and of the Diabetes Research Institute Federation (www.diabetesresearch.org).

In 2018 Ricordi was inducted into the National Academy of Inventors for contributing outstanding inventions that have made a tangible impact on quality of life, economic development, and welfare of society. That same year he was ranked as the #1 world expert in transplantation of insulin producing cells for treatment of diabetes, among over 4,000 physicians, surgeons and scientists evaluated. In 2019 Ricordi was appointed to the Supreme Council of Health (Consiglio Superiore di Sanita) by the Italian Ministry of Health.

Ricordi also serves as President of the Board of ISMETT (Mediterranean Institute of Transplantation and Advanced Therapies; http://www.ismett.edu), and was appointed President of Fondazione Ri.MED (http://www.fondazionerimed.eu) by the Italian Prime Minister, for the 2013-2017 term.

Ricordi was founding president of the Fondazione Cure Alliance ONLUS and of The Cure Alliance (www.thecurealliance.org) and Chairman of the Diabetes Research Institute Federation (http://www.diabetesresearch.org/Research-Collaboration), coordinating and promoting cure focused research at over 24 leading institutions worldwide, while further developing Telescience platform technologies to eliminate geographic barriers to scientific collaboration. These initiatives now allow scientists and project teams from around the world to synergize efforts and work together like if they are in the same physical space (https://www.corriere.it/cronache/19_febbraio_05/consiglio-superiore-sanita-n omine-7d42c47e-293e-11e9-950e-d545297d98ec.shtml).

Dr. Ricordi has been awarded 27 patents, has >1,000 scientific publications, >40,000 citations and a 95 H-index. Robert J. Stratta, MD, is Professor and Jesse H. Meredith Chair in Transplant Surgery and Director of Transplantation at Wake Forest Baptist Health, which is currently one of the largest kidney and pancreas transplant centers in the US. He also has a cross-appointment as a Professor both in Urology and with the Wake Forest Institute of Regenerative Medicine. He accepted this appointment in October 2001 following many years as Professor of Surgery and Director of Pancreas Transplantation at the University of Nebraska Medical Center and as Professor of Surgery at the University of Tennessee, Memphis. After earning his B.S. degree at the University of Notre Dame, Dr. Stratta received his M.D. degree from the University of Chicago-Pritzker School of Medicine and trained in General Surgery at the University of Utah. He then completed a transplant clinical and research fellowship at the University of Wisconsin-Madison. He is co-author of 6 books, 39 book chapters, 731 abstracts, 102 online commentaries, 423 oral presentations, and 439 peer-reviewed articles dealing predominantly with transplantation. He has accumulated more than $9 million in career research funding. He has been active in medical school, surgical resident, and transplant fellow education since 1988; is a member of 25 medical societies; three editorial and physician review boards each; and numerous local, regional, and national committees including United Network for Organ Sharing (UNOS) activities since 1988. His areas of research interest and expertise include kidney and pancreas allocation and transplantation, immunosuppressive strategies, organ donation and preservation, and expanded criteria donors. He is Past President of the Executive Board of Directors of Carolina Donor Services and was recently Councillor of UNOS Region 11 and a member of the UNOS Board of Directors. He has lectured worldwide on kidney and pancreas transplantation, has performed more than 2000 transplants in his career, is board certified in General Surgery, and has been selected as one of the Best Doctors in America since 1993, one of America's Top Surgeons since 2004, and is currently listed as one of Americas Top Doctors and the Patients Choice Award. Dr. Rainer W. G. Gruessner, MD, FACS, FICS, is Professor of Surgery at SUNY Downstate Health Sciences University. He formerly served as Chairmen of the Departments of Surgery at the University of Zurich, University of Arizona, and State University of New York. Dr. Gruessner is a nationally renowned surgeon and clinical innovator who has developed new surgical techniques for intestinal, pancreas, and liver transplants. He is prolific academic, a committed educator, and successful mentor to surgical and transplant faculty, residents and fellows. Dr. Gruessners academic accomplishments include more than 700 published manuscripts, review articles, book chapters, and published abstracts. Dr. Gruessner has been an invited speaker at over 170 institutions and meetings worldwide. Hes (co-) edited five textbooks: the standard textbooks on Transplantation of the Pancreas, Living Donor Transplantation, and Robotic Surgery and serving as senior editor of a textbook on Transplantation, Bioengineering and Regeneration of the Endocrine Pancreas and a textbook on Technological Advances in Surgery, Trauma and Critical Care. He has served as PI and co-investigator on over 20 research projects and clinical trials, supported by industry, foundations, and the NIH. Dr. Gruessner is a member of over 20 national and international professional societies, has organized many international congresses, is an editorial board member for about 10 journals and has served on many professional and societal committees. In 2019, he received the Richard C. Lillehei award from the International Pancreas and Islet Association (IPITA) for his lifetime achievements in the field of pancreas transplantation.