DOCSLIB.ORG

Phd Thesis Riccardo Sfriso

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Phd Thesis Riccardo Sfriso Graduate School for Cellular and Biomedical Sciences University of Bern ENDOTHELIAL CELL PROTECTION IN XENOTRANSPLANTATION AND ISCHEMIA/REPERFUSION INJURY: ASSESSING THE EFFECT OF MULTIPLE TRANSGENES AND THE PATHOPHYSIOLOGICAL ROLE OF THE PLASMA CASCADE SYSTEMS PhD Thesis submitted by Riccardo Sfriso from Italy for the degree of PhD in Biomedical Sciences Supervisor Prof. Dr. Robert Rieben Department for BioMedical Sciences Faculty of Medicine of the University of Bern Co-advisor Prof. Dr. Jörg Seebach Division of Immunology and Allergology University Hospital and Medical Faculty of the University of Geneva Accepted by the Faculty of Medicine, the Faculty of Science and the Vetsuisse Faculty of the University of Bern at the request of the Graduate School for Cellular and Biomedical Sciences Bern, Dean of the Faculty of Medicine Bern, Dean of the Faculty of Science Bern, Dean of the Vetsuisse Faculty Bern TABLE OF CONTENTS ABSTRACT ............................................................................................................................................ 1 INTRODUCTION ................................................................................................................................... 1 ORGAN SHORTAGE: THE SITUATION OF ALLOGENEIC ORGAN TRANSPLANTATION .......................................... 1 XENOTRANSPLANTATION: A POSSIBLE SOLUTION TO ORGAN SHORTAGE? ................................................... 3 CONCORDANT OR DISCORDANT XENOTRANSPLANTATION? ........................................................................ 5 THE HURDLES TO XENOTRANSPLANTATION. ORGAN REJECTION: PIG ORGANS ARE SEEN AS ‘DANGEROUS’ AND ‘FOREIGN’ BY THE HUMAN IMMUNE SYSTEM ............................................................................................. 6 Hyperacute rejection ..................................................................................................................... 7 Acute vascular rejection ................................................................................................................ 8 T-cell mediated rejection .............................................................................................................. 9 GENETIC MODIFICATION OF THE DONOR ................................................................................................ 11 CURRENT PRECLINICAL SURVIVAL OF XENOGRAFTS IN NON-HUMAN PRIMATE MODELS ............................... 15 THE COMPLEMENT SYSTEM AND ITS REGULATION ................................................................................... 16 Overview of the complement system .......................................................................................... 17 The classical pathway ................................................................................................................. 17 The lectin pathway ...................................................................................................................... 18 The alternative pathway .............................................................................................................. 18 C3 independent pathways .......................................................................................................... 19 Regulation of the complement system ....................................................................................... 19 THE COAGULATION SYSTEM ................................................................................................................. 22 THE VASCULAR ENDOTHELIUM: A KEY PLAYER IN REJECTION ................................................................... 24 Flow and shear stress ................................................................................................................. 25 The endothelial glycocalyx .......................................................................................................... 26 MICROFLUIDIC SYSTEM ....................................................................................................................... 30 HYPOTHESIS AND AIM OF THE THESIS .......................................................................................... 32 REFERENCES ..................................................................................................................................... 35 RESULTS ............................................................................................................................................. 51 PAPER I ............................................................................................................................................. 53 Assessment of the Anticoagulant and Anti-inflammatory Properties of Endothelial Cells Using 3D Cell Culture and Non-anticoagulated Whole Blood. ............................................................. 53 PAPER II ............................................................................................................................................ 61 3D artificial round section micro-vessels to investigate endothelial cells under physiological flow conditions. .................................................................................................................................. 61 PAPER III (BOOK CHAPTER) ................................................................................................................. 77 3D cell culture models for the assessment of anticoagulant and anti-inflammatory properties of endothelial cells .......................................................................................................................... 77 PAPER IV ........................................................................................................................................... 99 Release of pig leukocytes and reduced human NK cell recruitment during ex vivo perfusion of HLA-E/human CD46 double-transgenic pig limbs with human blood. ....................................... 99 PAPER V ......................................................................................................................................... 115 Multiple genetically modified GTKO/hCD46/HLA‐E/hβ2−mg porcine hearts are protected from complement activation and natural killer cell infiltration during ex vivo perfusion with human blood. ........................................................................................................................................ 115 PAPER VI ......................................................................................................................................... 127 Consistent success in life supporting porcine cardiac xenotransplantation ............................. 127 OVERALL DISCUSSION AND OUTLOOK ....................................................................................... 163 ACKNOWLEDGMENTS .................................................................................................................... 165 Abstract Worldwide, the critical and growing shortage of human donor organs represents a major concern which needs alternative solutions. Xenotransplantation – the transplantation of cells, tissues and organs between different species – has a long history and aims to provide a solution to the high demand of donor organs. Pigs are considered a suitable donor candidate, however organs from wildtype pigs are rapidly rejected by a process called hyperacute rejection. This consists of a massive antibody binding and subsequent complement activation with an inevitable graft destruction. Nowadays, hyperacute rejection can be overcome by genetic manipulation of the donor. However, a delayed rejection still occurs. It is defined as acute vascular rejection and is characterized by coagulation dysregulation resulting in thrombotic microangiopathy and leading to graft failure within days. Cellular rejection mediated by T cells as well as innate immune cells, including NK cells, macrophages and neutrophils is another hurdle which needs to be overcome in order to bring xenotransplantation closer to the clinical application. Advanced genetic engineering techniques such as the CRISPR-Cas9 technology allow to delete antigens from the porcine genome or to introduce human transgenes with the aim of reducing the molecular incompatibilities as well as the immunogenicity of the xenograft. The use of pigs with new multiple genetic modifications, including expression of human thrombomodulin, complement regulatory proteins and knock- out of xeno-antigens are now available for testing in nonhuman primates. This thesis focuses on the study of the vascular endothelium, as this is the first tissue to come in contact with the recipient blood after transplantation. A novel in vitro 3D microfluidic system has been developed and used to explore the effects of multiple transgenes in a xenotransplantation setting. Endothelial cells cultured on the luminal surface of circular microchannels were exposed to shear stress and pulsatile flow, so that they experience a microenvironment similar to the in vivo situation. Perfusion of porcine endothelial cells with human serum allowed to study the effects of transgenes on prevention of complement and antibody mediated cytotoxicity. This thesis comprises of interesting and fruitful collaborations which gave light to real breakthroughs in the field of xenotransplantation. Introduction Organ shortage: the situation of allogeneic organ transplantation Allogeneic organ transplantation – the transplantation between two genetically non- identical individuals
Load more

Recommended publications
  • The History of the First Kidney Transplantation
    165+3 14 mm "Service to society is the rent we pay for living on this planet" The History of the Joseph E. Murray, 1990 Nobel-laureate who performed the first long-term functioning kidney transplantation in the world First Kidney "The pioneers sacrificed their scientific life to convince the medical society that this will become sooner or later a successful procedure… – …it is a feeling – now I am Transplantation going to overdo - like taking part in creation...” András Németh, who performed the first – a European Overview Hungarian renal transplantation in 1962 E d i t e d b y : "Professor Langer contributes an outstanding “service” to the field by a detailed Robert Langer recording of the history of kidney transplantation as developed throughout Europe. The authoritative information is assembled country by country by a generation of transplant professionals who knew the work of their pioneer predecessors. The accounting as compiled by Professor Langer becomes an essential and exceptional reference document that conveys the “service to society” that kidney transplantation has provided for all mankind and that Dr. Murray urged be done.” Francis L. Delmonico, M.D. Professor of Surgery, Harvard Medical School, Massachusetts General Hospital Past President The Transplantation Society and the Organ Procurement Transplant Network (UNOS) Chair, WHO Task Force Organ and Tissue Donation and Transplantation The History of the First Kidney Transplantation – a European Overview European a – Transplantation Kidney First the of History The ISBN 978-963-331-476-0 Robert Langer 9 789633 314760 The History of the First Kidney Transplantation – a European Overview Edited by: Robert Langer SemmelweisPublishers www.semmelweiskiado.hu Budapest, 2019 © Semmelweis Press and Multimedia Studio Budapest, 2019 eISBN 978-963-331-473-9 All rights reserved.
    [Show full text]
  • Newsletteralumni News of the Newyork-Presbyterian Hospital/Columbia University Department of Surgery Volume 13, Number 1 Summer 2010
    NEWSLETTERAlumni News of the NewYork-Presbyterian Hospital/Columbia University Department of Surgery Volume 13, Number 1 Summer 2010 CUMC 2007-2009 Transplant Activity Profile* Activity Kidney Liver Heart Lung Pancreas Baseline list at year start 694 274 174 136 24 Deceased donor transplant 123 124 93 57 11 Living donor transplant 138 17 — 0 — Transplant rate from list 33% 50% 51% 57% 35% Mortality rate while on list 9% 9% 9% 15% 0% New listings 411 217 144 68 23 Wait list at year finish 735 305 204 53 36 2007-June 2008 Percent 1-Year Survival No % No % No % No % No % Adult grafts 610 91 279 86 169 84 123 89 6 100 Adult patients 517 96 262 88 159 84 116 91 5 100 Pediatric grafts 13 100 38 86 51 91 3 100 0 — Pediatric patients 11 100 34 97 47 90 2 100 0 — Summary Data Total 2009 living donor transplants 155 (89% Kidney) Total 2009 deceased donor transplants 408 (30% Kidney, 30% Liver) 2007-June 2008 adult 1-year patient survival range 84% Heart to 100% Pancreas 2007-June 2008 pediatric 1-year patient survival range 90% Heart to 100% Kidney or lung *Health Resource and Service Administration’s Scientific Registry of Transplant Recipients (SRTR) Ed Note. The figure shows the US waiting list for whole organs which will only be partially fulfilled by some 8,000 deceased donors, along with 6,600 living donors, who will provide 28,000 to 29,000 organs in 2010. The Medical Center’s role in this process is summarized in the table, and the articles that follow my note expand on this incredible short fall and its potential solutions.
    [Show full text]
  • Sex Glands, Vasectomy and the Quest for Rejuvenation in the Roaring Twenties
    122 Review Endeavour Vol.27 No.3 September 2003 ‘Dr Steinach coming to make old young!’: sex glands, vasectomy and the quest for rejuvenation in the roaring twenties Chandak Sengoopta School of History, Classics and Archaeology, Birkbeck College, University of London, Malet Street, Bloomsbury, London, UK WC1E 7HX In the 1920s, research on the endocrine glands – in the popular and medical press, but so-called organo- especially the sex glands – was widely expected to lead therapy with extracts of every conceivable tissue became to revolutionary new ways of improving human life. a fin-de-sie`cle panacea for virtually every conceivable The medical marketplace was crowded with glandular disorder [4]. It also stimulated a great deal of serious techniques to revitalize the aged. ‘Monkey glands’ experimental research on glandular functions. By the end apart, the Austrian physiologist Eugen Steinach’s simple, of the First World War, all this research had reached a vasectomy-like operation was perhaps the most popular critical mass. The ductless glands and their still mysteri- of these. Steinach was one of the leading endocrine ous secretions came to acquire an air of omnipotence in the researchers of the early 20th century and the Steinach 1920s. ‘We know definitely now,’ announced a popular Operation was based on rigorous laboratory research. It medical work of the 1920s, ‘that the abnormal functioning was much more than a simple scientific error, and its his- of these ductless glands may change a saint into a satyr; a tory shows us how early endocrine research was shaped beauty into a hag; a giant into a pitiful travesty of a human by broader social and cultural forces.
    [Show full text]
  • Cooperating Saves Lives Start Contents
    Annual Report 2019 Cooperating saves lives start contents Contents Foreword 1. The Eurotransplant community 2. Eurotransplant: donation, allocation, transplantation and waiting lists This document is optimized for Acrobat Reader for best viewing 3. Report of the Board and the central office experience. 4. Histocompatibility Testing Download Acrobat Reader 5. Reporting of non-resident transplants in Eurotransplant 6. Transplant programs and their delegates in 2019 A high resolution version of this document is also available. 7. Scientific output in 2019 Download high resolution pdf 8. Eurotransplant personnel related statistics 9. Abbreviated financial statements All rights reserved. No part of this publication may be reproduced, stored in a retrieval system List of abbreviations or transmitted, in any form or by any means, electronic, mechanical, photocopying or elsewise, without prior permission of Eurotransplant. For permissions, please contact: [email protected] start contents Foreword Dear reader, We are proud to offer you the 2019, digital edition of the International organ exchange Eurotransplant Annual Report. In this environmentally In 2019, 6981 organs from 2042 deceased donors were friendly, digital report you can easily browse via the used for transplantation for patients on the waiting top menu. Weblinks are added to facilitate in finding list of Eurotransplant. This decrease of the number of more specific information on relevant websites. The reported donors is 5,5% compared to 2018 (2159). report provides an overview of the key statistics on 21.5% of organs were exchanged cross-border between organ donation, allocation and transplantation in all the Eurotransplant member states. Thanks to this Eurotransplant countries. international exchange, a suitable donor organ could be You can also read in the report activities within found for many patients in the different Eurotransplant Eurotransplant that took place, decisions that were member states.
    [Show full text]
  • Analysis of the Trend Over Time of High-Urgency Liver Transplantation Requests in Italy in the 4-Year Period 2014-2017
    Analysis of the Trend Over Time of High-Urgency Liver Transplantation Requests in Italy in the 4-Year Period 2014-2017 S. Trapani*, F. Puoti, V. Morabito, D. Peritore, P. Fiaschetti, A. Oliveti, M. Caprio, L. Masiero, L. Rizzato, L. Lombardini, A. Nanni Costa, and M. Cardillo Italian National Transplant Center, Italian Institute of Health, Rome, Italy ABSTRACT Background. The national protocol for the handling of high-urgency (HU) liver organ procurement for transplant is administered by the Italian National Transplant Center. In recent years, we have witnessed a change in requests to access the program. We have therefore evaluated their temporal trend, the need to change the access criteria, the percentage of transplants performed, the time of request satisfaction, and the follow-up. Methods. We analyzed all the liver requests for the HU program received during the 4-year period of 2014 to 2017 for adult recipients (18 years of age): all the variables linked to the recipient or to the donor and the organ transplants are registered in the Informative Transplant System as established by the law 91/99. In addition, intention to treat (ITT) survival rates were compared among 4 different groups: (1) patients on standard waiting lists vs (2) patients on urgency waiting lists, and (3) patients with a history of transplant in urgency vs (4) patients with a history of transplant not in urgency. Results. Out of the 370 requests included in the study, 291 (78.7%) were satisfied with liver transplantation. Seventy-nine requests (21.3%) have not been processed, but if we consider only the real failures, this percentage falls to 13.1% and the percentage of satisfied requests rises to 86.9%.
    [Show full text]
  • Spain, France and Italy Are to Exchange Organs for Donation Chains
    Translation of an article published in the Spanish newspaper ABC on 10 October 2012 O.J.D.: 201504 Date: 10/10/2012 E.G.M.: 641000 Section: SOCIETY Pages: 38, 39 ----------------------------------------------------------------------------------------------------------------- This is what happened in Spain’s first ‘crossover’ transplant [For diagram see original article] Altruistic donor The chain started with the kidney donation from a ‘good Samaritan’ going to a recipient in a couple. The wife of the first recipient donated her kidney to a sick person in a second couple. The wife of the second recipient donated her kidney to a third patient on the waiting list. On the waiting list The final recipient, selected using medical criteria, was on the waiting list to receive a kidney from a deceased donor for three years. Spain, France and Italy are to exchange organs for donation chains ► The creation of this type of ‘common area’ in southern Europe will increase the chances of finding a donor match CRISTINA GARRIDO BRUSSELS | Stronger together. Although there are many things on which we find it difficult to agree, this time the strategy was clear. Spain, France and Italy have signed the Southern Europe Transplant Alliance to promote their successful donation and transplant system – which is public, coordinated and directly answerable to the Ministries of Health, as compared to the private models of central and northern Europe – to the international bodies. ‘We (Spain, France and Italy) decided that we had to do something together because we have similar philosophies, ethical criteria and structures and we could not each go our own way given how things are in the northern countries’, explained Dr Rafael Matesanz, Director of the Spanish National Transplant Organisation, at the seminar on donations and transplants organised by the European Commission in Brussels yesterday.
    [Show full text]
  • Value of Donor–Specific Anti–HLA Antibody Monitoring And
    CLINICAL RESEARCH www.jasn.org Value of Donor–Specific Anti–HLA Antibody Monitoring and Characterization for Risk Stratification of Kidney Allograft Loss † †‡ | Denis Viglietti,* Alexandre Loupy, Dewi Vernerey,§ Carol Bentlejewski, Clément Gosset,¶ † † †‡ Olivier Aubert, Jean-Paul Duong van Huyen,** Xavier Jouven, Christophe Legendre, † | † Denis Glotz,* Adriana Zeevi, and Carmen Lefaucheur* Departments of *Nephrology and Kidney Transplantation and ¶Pathology, Saint Louis Hospital and Departments of ‡Kidney Transplantation and **Pathology, Necker Hospital, Assistance Publique Hôpitaux de Paris, Paris, France; †Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale, UMR-S970, Paris, France; §Methodology Unit (EA 3181) CHRU de Besançon, France; and |University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania ABSTRACT The diagnosis system for allograft loss lacks accurate individual risk stratification on the basis of donor– specific anti–HLA antibody (anti-HLA DSA) characterization. We investigated whether systematic moni- toring of DSA with extensive characterization increases performance in predicting kidney allograft loss. This prospective study included 851 kidney recipients transplanted between 2008 and 2010 who were systematically screened for DSA at transplant, 1 and 2 years post-transplant, and the time of post– transplant clinical events. We assessed DSA characteristics and performed systematic allograft biopsies at the time of post–transplant serum evaluation. At transplant, 110 (12.9%) patients had DSAs; post- transplant screening identified 186 (21.9%) DSA-positive patients. Post–transplant DSA monitoring im- proved the prediction of allograft loss when added to a model that included traditional determinants of allograft loss (increase in c statisticfrom0.67;95%confidence interval [95% CI], 0.62 to 0.73 to 0.72; 95% CI, 0.67 to 0.77).
    [Show full text]
  • April 2–6, 2008 Gaylord Texan, Dallas, Texas Spring
    Spring ’08 Clinical Meetings April 2–6, 2008 Gaylord Texan, Dallas, Texas JC A[[fkfm_j^A;;F <_dZekj^emj^[DWj_edWbA_Zd[o<ekdZWj_edÊi A_Zd[o;Whbo;lWbkWj_edFhe]hWcYedj_dk[i je[nfWdZ$$$ @::E^hi]ZaVg\ZhiYZiZXi^dcegd\gVb^ci]Z Jc^iZYHiViZh[dg`^YcZnY^hZVhZ# BdgZi]Vc&%%!%%%eVgi^X^eVcih @::E^h[daadl^c\"jel^i]eVgi^X^eVcihdkZg VcZmiZcYZYeZg^dYd[i^bZ# <adWVaZmeVch^dcd[@::E^hjcYZglVn# B[Whdceh[WXekjA;;F m^_b[oekWh[Wjj^[Yed\[h[dY[$ &# K^hijhVii]ZC@;Wddi],&.[dgi]ZaViZhi^c[dgbVi^dc# '#?d^cjh[dgV[gZZ8B:7gZV`[VhiHnbedh^jb^c<gVeZk^cZ8 dcHVijgYVn!6eg^a*!'%%-[gdb+/%%VbÄ-/%%Vb/ Æ8]gdc^X@^YcZn9^hZVhZ>ciZgkZci^dch/ >begdk^c\8@9VcY8K9DjiXdbZh#Ç (# K^Zli]ZaViZhi@::EYViVWZ^c\egZhZciZY^c&&edhiZgh Yjg^c\i]ZedhiZghZhh^dc#Add`[dgedhiZgcjbWZgh/)*!*(! +)!,*!,,!,-!'%*!',%!'-'!'-(VcY'-.# NdjXVcVahdk^h^ia[[fedb_d[$eh][dgi]ZaViZhi@::E^c[dgbVi^dcVcYVhX]ZYjaZd[ hXgZZc^c\hVXgdhhi]ZJ#H# www.keeponline.org '%%-CVi^dcVa@^YcZn;djcYVi^dc!>cX#6aag^\]ihgZhZgkZY#%'"(*"),(6 Prints: 4C — Live Size: 8"w x 11"h Size:Trim 9"w x 12"h Bleed Size: 9.25"w x 12.25"h Ad PGF-0288 AST Abstracts/American of Journal Transplantaion Mechanical resized from by PGF-0163 CF •C •M •Y •Y •K Your Partner in Transplantation At Astellas, we are committed to uncovering new possibilities in immunology through broad scale research aimed at new product development. Through the transference and sharing of scientifi c knowledge, we work in partnership with healthcare professionals like you to positively impact patient care. Our goal remains clear: Enhance the practice of transplantation.
    [Show full text]
  • 2015 UNOS Transplant Mangement Forum Abstracts
    ABSTRACTS 2015 UNOS Transplant Management Forum, San Diego, CA CATEGORY 1 Cost Reduction/Increase in Work Efficiency/Patient Care Safety Programs ABSTRACT C1-A FEASIBILITY OF REMOTE MONITORING OF VITAL SIGNS AMONG KIDNEY TRANSPLANT RECIPIENTS Stephen Pastan, MD, Emory Transplant Center, Atlanta, GA Purpose: We conducted a pilot study of in-home monitoring in a cohort of renal transplant patients to determine the feasibility of remotely monitoring vital data, and to identify abnormal values that could be intervened upon early to avoid hospital readmissions. The use of in-home "hovering" technologies, which can remotely transmit relevant clinical data, has been associated with decreased readmission rates and reduced costs in other patient populations. However, no study has examined the impact of a hovering platform in post-kidney transplant patients – a population at high-risk for readmissions. Methods: A cohort of adult kidney transplant recipients within 12 months of transplant were identified by transplant center coordinators and providers, and were given the hovering platform equipment during a post-transplant clinic visit. Patients were trained on equipment setup and use by study staff and were instructed to measure blood pressure, pulse oxygen, weight, temperature, and blood sugar levels (if diabetic) for 1 to 3 months. Except for the thermometer and glucometer, devices were connected via blue tooth to a main hub. Vital measurements were transmitted to the hub and automatically downloaded by cell or land-line to a software program that was monitored daily by study staff. In the case of an abnormal reading, study staff notified the patient’s nurse and/or physician, who contacted the patient and intervened as necessary.
    [Show full text]
  • Eurotimes 11-1 1-20
    10 years By Nick Lane PhD Pioneers Past and Present – But where are the boundaries of the justifiable? heir names justly echo down the halls Elder, his colleagues walked out of early example was the supplanting of horse- “I don’t think for a moment that we’re Tof fame of ophthalmology – Sir presentations; the very concept of IOL drawn carriages by cars; there were many going to see the end of LASIK or corneal Harold Ridley, Peter Choyce, Cornelius implantations was openly repudiated, and people at the time who could see no refractive surgery in general, but as the Binkhorst, Edward Epstein, Svyatoslav dismissed by the AAO as “not sufficiently advantages of cars over horses,” Dr Fine new generations of accommodating IOLs Fyodorov, Charles Kelman, Benedetto proven for use in the US”. Ridley spent told EuroTimes. come into their own, we’re likely to see Strampelli, José Barraquer, Luis Ruiz,Theo years terrified that his early failures would Of course pioneers need more than just more and more people in their fifties and Seiler, Ioannis Pallikaris, to take just a few. come back to haunt him through the vision to succeed; they also need the sixties opting for lens exchange, maybe Their techniques transformed the world courts. In Barcelona, in 1970, Joachim ability to see a technical way through the even before they’ve developed the first and restored sight for millions. But had it Barraquer was forced to explant half of problem, to convert their vision into signs of a cataract.This is not really a not been for their failures, the successes the anterior IOLs that he had implanted in action.And they need to be able to get it technical leap, at least not surgically – it is of today might never have been possible.
    [Show full text]
  • Anhang 1 Eurotransplant International Foundation
    Anhang 1 Eurotransplant International Foundation A m 1. Dezember 1997 trat in der Bundesrepublik Deutschland das Gesetz über die Spende, Entnahme und Übertragung von Organen, kurz Transplantationsgesetz (TPG) genannt, in Kraft. Es regelt neben den Voraussetzungen für eine Organspende auch die Verteilung der verfügbaren vermittlungspflichtigen Or- gane (Herz, Lunge, Leber, Niere, Bauchspeicheldrüse, Dünn- darm). Hierzu führt es in § 12(3) aus, dass die vermittlungs- pflichtigen Organe von einer Vermittlungsstelle nach Regeln, die dem Stand der Erkenntnisse der medizinischen Wissen- schaft entsprechen, insbesondere nach Erfolgsaussicht und Dringlichkeit für geeignete Patienten zu vermitteln sind. Die gemeinnützige Stiftung Eurotransplant Foundation (ET) in Lei- den/Niederlande (www.eurotransplant.nl) wurde vom Gesetz- geber mit der Wahrnehmung der Aufgabe der Vermittlungsstel- le beauftragt. Neben der Vermittlungsstelle sieht der Gesetzgeber im TPG auch die Einrichtung einer Koordinierungsstelle – wahrgenom- men von der Deutschen Stiftung für Organtransplantation (DSO) – zur Koordinierung aller Aspekte der Organsspende vor. ET ist eine 1967 von dem Transfusionsmediziner Jon van Rood ins Leben gerufene Non-Profit-Organisation. Van Rood erkannte die grundlegende Bedeutung des HLA-Systems für die allogene Organtransplantation und regte an, das HLA von Spen- der und Empfänger bei Zuteilung von Organtransplantaten, ins- besondere bei der Nierentransplantation, zu berücksichtigen. Um über einen größeren Pool an Spendern und Empfängern zu verfügen und somit eine optimierte Organzuteilung zu errei- 172 z Anhang 1 Eurotransplant International Foundation chen, wurde ein erster europäischer Transplantationsverbund von den Ländern Belgien, Niederlande, Luxemburg und Deutschland gegründet. Dieser wurde 1971 durch Österreich und im Jahr 2000 durch den Beitritt von Slowenien erweitert. ET ist eine gemeinnützige Stiftung, die von den beteiligten Staaten bzw.
    [Show full text]
  • The History of Kidney Transplantation: Past, Present and Future (With Special References to the Belgian History)
    1 The History of Kidney Transplantation: Past, Present and Future (With special references to the Belgian History) Squifflet Jean-Paul University of Liege Belgium 1. Introduction The history of kidney transplantation is thought to have originated at the early beginning of the previous century with several attempts of Xenografting, and experimental works on vascular sutures (Küss & Bourget, 1992)1. But it really started more than 60 years ago with first attempts of deceased donor transplantation (DCD) and the first successful kidney transplantation of homozygote twins in Boston (Toledo-Pereyra et al, 2008)2. Belgian surgeons contributed to that field of medicine by performing in the early sixties the first ever organ procurement on a brain dead heart beating donor (DBD) (June 1963) (Squifflet, 2003)3. Later on, in the eighties, they published a first series of living unrelated donor (LURD) transplantations, as well as ABO-Incompatible living donor (ABO-Inc LD) transplantations. With the advent of Cyclosporine A, and later other calcineurin inhibitors such as Tacrolimus, with the advent of more potent immunosuppressive drugs (IS), the gap between the number of renal transplant candidates and the number of transplanted recipients was and is continuously increasing in Belgium and most countries. It opened the search for other sources of organs such as donors after cardiac death (DCD) defined with the Maastricht conference and the extended criteria donors (ECD) compared to standard criteria donors (SCD). In Belgium another source of DCD was identified after the promulgation in 2002 of a law on euthanasia. The Belgian example and all its historical measures could help others to fight against organ shortage and its consequences, organ trafficking, commercialization and tourism.
    [Show full text]