25th Anniversary of the Islet Bank • Isolation of Islets of Langerhans for Transplantation in Diabetic Patients
by Michel van der Burg, Monday 24 August 2026
Abstract
This account documents the establishment of the Dutch Islet Bank at Leiden University Medical Center (LUMC) between 1997 and 2003. Following a 1997 mandate from Onno Terpstra to develop a clinical islet transplantation programme, and a 1998 working visit to the Diabetes Research Institute in Miami to learn state-of-the-art human islet isolation from their team, during which he also tested the Iodixanol-UWS purification method, the author set up the Clinical Islet Laboratory (Klinisch Eilandjeslaboratorium, KEL) within LUMC’s new GMP facility, opened in February 2000. Between 2000 and 2001, the isolation procedure was upgraded to the automated “Ricordi Method” and a clinical-grade Iodixanol-UWS purification method, Standard Operating Procedures were drafted and reviewed, and permit applications were submitted to the Medical Research Ethics Committee and the Dutch Healthcare Insurance Board (CVZ). The Clinical Islet Laboratory began operating under cGMP conditions in April 2001, followed in September 2001 by CVZ’s positive advice on permits for both islet production and transplantation. Collaboration with the Geneva and Edmonton islet teams in 2001–2002, amid heightened interest following the Edmonton Protocol’s 2000 publication, informed further refinement of the isolation procedure. Formal government approval for the islet bank followed in 2003, culminating in its official establishment via ministerial regulation on 5 December 2003. Clinical islet transplantation itself began at LUMC in late 2007, following restructuring and team expansion; more than 100 transplantations have since been performed in over 50 patients. The account closes by noting that LUMC’s current automated islet-production method still relies on the iodixanol-related purification approach the author introduced three to four decades earlier.
Citation info : 2001 — Establishing the Dutch Islet Bank in the LUMC • 1MEMO_20260824 • Michel van der Burg • Miracles.Media • URL https://michelvanderburg.com/2026/08/24

2001 — Establishing the Dutch Islet Bank in the LUMC
Plan
In 1997, Onno Terpstra, Head of Surgery at Leiden University Medical Center (LUMC), asked me (Michel van der Burg) to develop a plan for a clinical islet isolation and transplantation programme (1). Islet transplantation was at the time practised at only a handful of centres worldwide, and building such a programme from scratch meant starting not with patients but with technique. In 1998, I undertook a working visit to the Diabetes Research Institute in Miami, then among the world’s leading centres for human islet isolation, to learn state-of-the-art isolation methods directly from their team. During this visit I also tried the Iodixanol-UWS purification method, a density-gradient approach I had just recently developed in animal experimental research in Leiden, that later became a recurring part of my work in the field, though its longer-term relevance wasn’t clear at the time (2).
Back in Leiden, I began the islet isolation programme at the LUMC with my Surgery co-workers, and the setting-up of the Clinical Islet Laboratory (Klinisch Eilandlaboratorium, KEL) in the new GMP facility then being build at the LUMC, in collaboration with Amon Wafelman, executive head of the future GMP facility. A business plan, submitted to the LUMC Board of Directors in November 1998 , was approved on February 22, 1999 — formally launching our LUMC islet transplantation project.
Surgery Laboratory
In March 1999, a first experimental series of islet isolations was started, applying the manual method of donor pancreas digestion and purification of the islets in our new Iodixanol-UWS gradients. With the approval of the Board of Directors — since the GMP facility was still under construction — work began in our Surgery Laboratory, gaining hands-on experience with human islet isolation, the donor procedure, islet culture, and all other facets of operating an “islet bank.”

Opening GMP Facility
On 22 February 2000, exactly one year after the official start of our islet transplantation project (1), the GMP facility of the LUMC was officially opened — the centre with six special laboratory spaces, the “cleanrooms,” for the Good Manufacturing Practice (GMP) preparation of Immuno, Cell, and Gene Therapy products (3).

As coordinator of the LUMC Clinical Islet Laboratory (“Klinisch Eilandjeslaboratorium”), I presented our project for the GMP production of clinical-grade islets in a talk that day during the symposium “The Interdivisional GMP Facility LUMC, a vital link between bench and bedside in Immuno, Cell, and Gene Therapy”, to an audience of LUMC staff and government representatives, including the Ministry (4).
Slideshow (video & audio) — Isolation of Islets of Langerhans for Transplantation in Diabetic Patients • Symposium GMP Facility LUMC 2000 • Michel van der Burg • Miracles.Media • 1 MEMO_20260824_1
Video of the slideshow of this talk was previously posted online in 2019 (4).
Here video is posted of the remastered second edition (2026) of the slideshow, now also with audio reading the original transcript using my personal synthesised voice, and supplemented with a few notes including the symposium programme. Handout available in Notes (4).
From 2000 onward, following the opening of the new GMP facility, the laboratory adopted the state-of-the-art “Ricordi Automated Method” for pancreas digestion and islet isolation (named for Camillo Ricordi’s semi-automated digestion chamber, by then fairly standard in the field), using equipment supplied through BioRep Technologies in Miami (5).
Standard Operating Procedures (SOPs) & Permit application
This shift prompted the drafting of (i) the ‘core’ SOPs (the Standard Operating Procedures for the isolation and storage of islets) for review by GMP deputy head Wafelman, (ii) the training of Surgery research co-workers for the islet isolation team, and (iii) the drafting of the “Transplantation Pancreatic Islets Protocol” (6) for our Permit Application (7) co-authored with surgeons Jan Ringers (head of the transplant section) and our head and supervisor, Onno Terpstra.
In July 2000 , we submitted our transplant protocol (6) for review to the Medical Research Ethics Committee , and our ‘Permit Application Transplantation of Islets of Langerhans’ (7) to the Dutch Healthcare Insurance Board (College voor Zorgverzekeringen; CVZ) now the National Health Care Institute of the Netherlands, advising the Ministry of Health, Welfare and Sport (VWS).

In July 2000, our new series of islet isolations began, assisted by our Surgery islet isolation team, using the automated method for pancreas digestion, and islet purification with “IsletPrep” — our new Iodixanol-UWS islet purification solution. This new solution had a slightly modified composition, in preparation for the planned commercial production of the solution as the GMP-certified, ready-made product “IsletPrep” (5, 8).
By the end of 2000, we had gained sufficient experience in carrying out our procedures for human islet isolation, and all our SOPs were reviewed together with GMP head Wafelman (9), so that work could continue in the GMP facility. This revealed that our existing procedure for purifying the islets in Iodixanol-UWS needed to be adapted — a procedure for which we had used in-house-produced “IsletPrep,” a reformulated Iodixanol-UWS solution developed together with Nycomed/Axis-Shield (8).

As GMP production of IsletPrep would not be ready in time for the planned start of work in the GMP Facility in early 2001, we validated a simpler alternative combining clinical-grade Visipaque and ViaSpan, which matched IsletPrep’s results in islet purification (5). This Visipaque-ViaSpan protocol became the standard, enabling the opening of the LUMC’s Clinical Islet Laboratory (Klinisch EilandLaboratorium) in April 2001.

2001 – Opening Islet Bank in GMP-Facility
On Thursday 26 April 2001, I was able to open the Clinical Islet Laboratory (“Klinisch Eilandjeslaboratorium”) in the GMP Facility of the LUMC, enabling islet isolation to be carried out under cGMP conditions from then on.
Our standard operating procedure for clinical-grade islet production comprised (i) preparation of the donor pancreases in the operating theatre of the LUMC, including collagenase infusion, followed by (ii) transport of the pancreata to the nearby cleanroom of the Clinical Islet Laboratory in the LUMC GMP Facility for (iii) islet production: the isolation, purification, storage, and quality control of the isolated human islets.

In July 2001, we received the green light from GMP head Wafelman for the delivery of a cGMP-certified islet preparation meeting our criteria for transplantation, subject to obtaining approval from the Medical Research Ethics Committee and the Board of Leiden University Medical Center.

On 27 September 2001, the positive advice also followed from the Dutch Healthcare Insurance Board (College voor Zorgverzekeringen) (CVZ), now the National Health Care Institute of the Netherlands, issued to the Ministry of Health, Welfare and Sport, to grant permission for Transplantation of Islets of Langerhans at Leiden University Medical Center. Their advice to the Cabinet Minister in fact included two permits for the LUMC, covering both islet production and transplantation:
1) a permit for the Dutch Islet Bank in the LUMC (for the production and storage of islets in our Clinical Islet Laboratory, “Klinisch Eilandjeslaboratorium”);
2) and also the permit to transplant islets from the islet bank into patients at the LUMC.
The report is available for reading and downloading below in the References section (10).

Implementation of the Edmonton Protocol — ITN Trial
By this time, expectations surrounding islet transplantation were running high, after the Edmonton team (University of Alberta, Edmonton, Canada) reported in the 27 July 2000 issue of ‘The New England Journal of Medicine’ their initial findings with up to a year of follow-up in seven consecutive subjects treated with infusion of an adequate mass of freshly prepared islets from two or more donor pancreases, combined with a steroid-free immunosuppression regimen. In all seven subjects, insulin independence was achieved, with tight glycemic control and correction of glycated hemoglobin levels (18). This treatment became known as the Edmonton protocol.

I was collaborating on our Iodixanol-UWS purification procedure with surgeon José Oberholzer of the Geneva islet team, who had invited me for a working visit to their islet centre. In July 2001, I shadowed the Geneva team during the islet isolations they performed according to the successful Edmonton procedure, as part of a multicentre International Trial of the Edmonton Protocol (ITN).

José Oberholzer and his co-worker Raymond Mage, together with Jonathan Lakey of the Edmonton centre (Edmonton, Canada), subsequently helped me in 2002 with the further development of our isolation procedure, incorporating the ITN procedures into the 2nd edition of our SOPs (11), and with custom-made apparatus — a gradient mixer — for purifying islets in continuous density gradients in the Cobe centrifuge.

2003 — Official Establishment of the Dutch Islet Bank
On 22 May 2003, the Healthcare Inspectorate (Inspectie Gezondheidszorg) — at the request of the Ministry of VWS — inspected the Islet Bank in the GMP facility of the LUMC and our Standard Operating Procedures (SOPs), and decided to advise the Minister favourably on our permit application (“Eilandjesbank,” Onno Terpstra, Surgery, LUMC email newsletter, 22 May 2003); in August 2003, the Ministry’s approval of our islet bank followed (12).
“Breakthrough for diabetes • At the end of August, the Ministry of Health, Welfare and Sport (VWS) granted permission to the Department of Surgery at the LUMC for the storage of so-called ‘islets of Langerhans’. These small glands from the pancreas contain insulin-producing cells that help maintain blood sugar levels. A decision regarding the application to actually transplant these islets into diabetes patients will follow shortly. This groundbreaking treatment method stands alongside the treatment applied almost exclusively at the LUMC for patients with diabetes, in which both a donor kidney and a pancreas can be transplanted.” — Source : Cicero, September 12, 2003 (13)
Finally, the official establishment of the Dutch Islet Bank at the LUMC followed on 5 December 2003, with the publication on 3 December 2003 in the Government Gazette of the Kingdom of the Netherlands (Staatscourant 2003, 234, p. 31) of the ‘Regulation on the Transplantation of Islets of Langerhans’ (Dutch: ‘Regeling transplantatie eilandjes van Langerhans’) issued by the Minister of Health, Welfare and Sport on 25 November 2003, no. IBE 2431923.
The regulation is available for viewing and downloading in the Notes (14).

Quote (translated)
“… the Leiden University Medical Center will be granted permission to start transplantation of islets of Langerhans immediately.”
— The Minister of Health, Welfare and Sport, J.F. Hoogervorst
25th Anniversary of the Islet Bank
The year 2026 marks the 25th anniversary of the islet bank, started by Michel van der Burg and his Surgery co-workers on Thursday 26 April 2001 as the “Clinical Islet Laboratory” (Dutch: Klinisch Eilandjeslaboratorium) in the GMP Facility of the LUMC.
Islet Transplantation
In the early years, prior to the permit for the islet bank, the small Surgery islet team did not yet have access to donor organs that were both qualitatively suitable and quantitatively sufficient for islet transplantation.
For the transition to the future transplantation programme — with continuous, 24/7 islet production in the islet bank from as many suitable organs as possible — expanding the isolation teams’ staffing in the islet bank was now the highest priority.
Following the granting of the permit for the islet bank, the islet transplantation project was restructured from 2004 onwards, so that, under a new board drawn from the various divisions of the LUMC, a new and larger isolation team for the islet bank could be assembled. With that new team in the islet bank, islet transplantation could begin at the LUMC from the end of 2007 onwards, and more than 100 islet transplantations have since been carried out in more than 50 patients (15, 16).

Today, the LUMC islet bank works with a further-developed automated procedure for the machine-based production of islets (17). It gives me great satisfaction to see that this once again involves collaboration with BioRep Technologies in Miami, and that the purification method I introduced some 30–40 years ago is once again the method of choice — using iopromide (Ultravist 370), related to iodixanol, and the UWS organ preservation fluid introduced for islet isolation and purification in 1989.
Notes
References
1) 1999 — Pioneering the LUMC Clinical Islet Transplant Project • 1MEMO_20260705 • Michel van der Burg • Miracles•Media • URL https://michelvanderburg.com/2026/07/05
2) Human Islet Isolation • DRI Miami 1998 • 1MEMO_20250204 • Michel van der Burg • Miracles.Media• TakeNode 86e4a319-a769-44d5-8fa5-de2ca90ab63c • URL https://michelvanderburg.com/2025/02/04/
3) Cicero • 1MEMO_20260824_2_2 • Miracles.Media • Feature story ‘Schoner kán het niet’ (It doesn’t get any cleaner than this) by Elmar Veerman in the LUMC news magazine Cicero, 25 February 2000 (ISSN 0920-2900) . Article for viewing and download below (1MEMO_20260824_2_2.pdf)
4) Michel P.M. van der Burg . Isolation of islets of Langerhans for transplantation in type-1 diabetic patients. Symposium ‘The Interdivisional GMP Facility LUMC, a vital link between bench and bedside in Immuno, Cell, and Gene Therapy’. Leiden (Netherlands) Februari 22, 2000 .
Video of slideshow presentation : Isolation of Islets of Langerhans for Transplantation in Diabetic Patients • Symposium GMP Facility LUMC 2000 • Michel van der Burg • Miracles.Media • 1MEMO_20260824_1_Video • TakeNode 976e1d79-8cc6-4348-8ecb-c3ffb34c2f57
Handout of slideshow presentation • 1MEMO_20260824_1_Handout • TakeNode 717f2297-0a93-4d99-8deb-0eb809cf21e4 • Available for viewing and download below .
PS – First video edition of the slideshow posted in 2019 : Isolation of Islets of Langerhans for Transplantation in Type-1 Diabetic Patients • 1MEMO_20191213 • Michel van der Burg • Miracles.Media • URL https://michelvanderburg.com/2019/12/13/
5) 2000 — Pioneering Automated Islet Isolation & Clinical Grade Purification in the LUMC • 1MEMO_20260720 • Michel van der Burg • Miracles•Media • URL https://michelvanderburg.com/2026/07/20
6) Transplantatie van pancreaseilandjes – Protocol (tr. Transplantation Pancreatic Islets Protocol) by Jan Ringers and Michel van der Burg (JR / MvdB / 07 ; edition 7 , date 15 May 2000). In : LUMC Vergunningsaanvraag Transplantatie Eilandjes van Langerhans (7,10).
7) LUMC Vergunningsaanvraag Transplantatie Eilandjes van Langerhans (LUMC Permit Application Transplantation of Islets of Langerhans) , In (Bijlage 1) : Advies vergunningsaanvraag transplantatie Eilandjes van Langerhans , College voor Zorgverzekeringen, 27 September 2001 (CVZ , Rapport 01/71). Download available below (10).
8) Islet purification from bench to bedside • @1MEMO_20260623 • Michel van der Burg • Miracles.Media • URL https://michelvanderburg.com/2026/06/23/
9) GMP Documentation Clinical Islet Laboratory (Klinisch Eilandjeslaboratorium) LUMC , 1st edition (December 2000) by Michel van der Burg , Department of Surgery , LUMC.
10) Advice LUMC Permit Dutch Healthcare Insurance Board CVZ 01/71 • 1MEMO_20260824_5_ebook • Miracles.Media • TakeNode 5b2238fc-0f44-4523-8e7e-a084a5f193de • The September 2001 advice of the dutch National Health Care Institute issued to the Ministry of Health, Welfare and Sport, to grant permission for the islet bank and for islet transplantation in the LUMC In : Advies vergunningsaanvraag transplantatie Eilandjes van Langerhans , College voor Zorgverzekeringen, 27 September 2001 (CVZ , Rapport 01/71). Preview and download e-book below (1MEMO_20260824_5_ebook.pdf).
11) GMP Documentation Clinical Islet Laboratory (Klinisch Eilandjeslaboratorium) LUMC , 2nd (revised) edition 8 May 2002, by Michel van der Burg , Department of Surgery , LUMC • 1MEMO_20260824_CITX_20020508 • Michel van der Burg • Miracles.Media • TakeNode • E-book copy (1MEMO_20260824_CITX_20020508.pdf) available on request.
12) Nier plus klier werkt beter (Kidney plus gland works better) by Willy van Strien in the LUMC news magazine Cicero #14, 12 September 2003 (ISSN 0920-2900)
13) Doorbraak voor diabetes • Cicero 12 September 2003 • 1MEMO_20260824_11 • Michel van der Burg • Miracles.Media • TakeNode fe71b42f-f1ff-49c3-8668-ee8ce4c8b636 • Source : Archive Michel van der Burg • Miracles.Media : Screenshot LUMC website retrieved 12 January 2006.
Transcript :
“Doorbraak voor diabetes | Het ministerie van VWS heeft eind augustus toestemming gegeven aan de afdeling Heelkunde van het LUMC voor de opslag van zogenaamde ‘eilandjes van Langerhans’. Deze kliertjes uit de alvleesklier bevatten insuline producerende cellen die helpen bij het op peil houden van de bloedsuikerspiegel. Binnenkort volgt uitspraak over de aanvraag om deze ellandjes ook daadwerkelijk te gaan transplanteren bij diabetes patlenten. Deze baanbrekende behandelmethode staat naast de bijna alleen in het LUMC toegepaste behandeling bij patlenten met suikerzlekte waarbij zowel een donornier als een alvleesklier kan worden getransplanteerd. Bron: Cicero, 12 september 2003”

14) Regulation transplantation islets of Langerhans • Regulation of the Minister of Health, Welfare and Sport of 25 November 2003, no. IBE 2431923 • In : ‘Regeling transplantatie eilandjes van Langerhans’ van de Minister van Volksgezondheid, Welzijn en Sport van 25 november 2003, nr. IBE 2431923 . Staatscourant 2003, 234, p. 31 . Published 3 December 2003. (Retrieved 20 August 2026) URL https://zoek.officielebekendmakingen.nl/stcrt-2003-234-p31-SC62493.html • View and download copy of Regulation below (file stcrt-2003-234-p31-SC62493.pdf ).
Quote (translated)
“… the Leiden University Medical Center will be granted permission to start transplantation of islets of Langerhans immediately.”
—The Minister of Health, Welfare and Sport, J.F. Hoogervorst
Dutch original
“…zal aan het Leids Universitair Medisch Centrum vergunning worden verleend om nu al te starten met transplantatie van eilandjes van Langerhans.”
—De Minister van Volksgezondheid, Welzijn en Sport, J.F. Hoogervorst
15) Berney T, Andres A, Bellin MD, de Koning EJP, Johnson PRV, Kay TWH, Lundgren T, Rickels MR, Scholz H, Stock PG, White S and the International Islet Transplant Centers (2022) A Worldwide Survey of Activities and Practices in Clinical Islet of Langerhans Transplantation. Transpl Int 35:10507. doi: 10.3389/ti.2022.10507 .
URL (retrieved 22 August 2026) https://www.frontierspartnerships.org/journals/transplant-international/articles/10.3389/ti.2022.10507/full

16) Islet transplantation (Eilandjestransplantatie). LUMC, Patient information leaflet (retrieved 22 August 2026) • URL https://www.lumc.nl/afdelingen/transplantatie-centrum/diagnoses-en-behandelingen/eilandjestransplantatie/
17) Doppenberg JB, Engelse MA, de Koning EJP. PRISM: A Novel Human Islet Isolation Technique. Transplantation. 2022 Jun 1;106(6):1271-1278. doi: 10.1097/TP.0000000000003897. Epub 2022 Jul 22. PMID: 34342959. URL https://www.ovid.com/jnls/transplantjournal/fulltext/10.1097/tp.0000000000003897~prism-a-novel-human-islet-isolation-technique
18) Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med. 2000 Jul 27;343(4):230-8. doi: 10.1056/NEJM200007273430401. PMID: 10911004. URL https://www.nejm.org/doi/full/10.1056/NEJM200007273430401 . Paper copy URL https://www.ualberta.ca/en/alberta-diabetes/media-library/about/documents/nejmedmontonprotocol.pdf
Acknowledgements — I thank Camillo Ricordi (Director of the Diabetes Research Institute, Miami) and Ramon Poo (BioRep Technologies, Miami), Daniel Brandhorst (Giessen, Germany), José Oberholzer and co-workers (Geneva, Switzerland), and Jonathan Lakey (Edmonton, Canada) for their help in implementing their state-of-the-art islet isolation procedures in our Clinical Islet Laboratory; Onno Terpstra ((Head of the Surgery department) , Amon Wafelman (deputy head of the Interdivisional GMP-Facility, Department of Clinical Pharmacy and Toxicology, LUMC) and the numerous LUMC co-workers from other LUMC departments for collaboration in establishing the Clinical Islet Laboratory; our Transplant Coordinators Marijke van Gurp and Ruth Dam (EuroTransplant/LUMC) and my co-workers of the Transplant section of the Surgery Department (LUMC) : surgeons Jan Ringers, André Baranski, Jeroen Dubbeld, Xandro Schaapherder for dedicated organ procurement, and the researchers Eelco Bouwman, Annemiek Töns (staff) and Josephine Rijkelijkhuizen, Gabe Bleeker (students) for our collaboration in the ‘islet team.’
#islets #islet #Langerhans #isolation #automated #purification #ITN #Edmonton #bank #surgery #clinical #laboratory #establishment #start #GMP #SOP #eilandjes #transplantatie #eilandjestransplantatie #cleanroom #facility #Surgery #KEL #CITX #LUMC #VWS #vergunning #regeling #Holland #Netherlands #Leiden #university #hospital #human #donor #IsletPrep #Visipaque #Optiprep #iodixanol #ViaSpan #UWS #density #gradient #pancreas #transplantation #diabetes #history #research #memoir #1memo #michelvanderburg #Klinisch #Eilandlaboratorium #BioRep #Ricordi #Geneva #Oberholzer
Portfolio Science Posts
https://michelvanderburg.com/category/science/
Citation info : 2001 — Establishing the Dutch Islet Bank in the LUMC • 1MEMO_20260824 • Michel van der Burg • Miracles.Media • URL https://michelvanderburg.com/2026/08/24