2000 — Pioneering Automated Islet Isolation & Clinical Grade Purification in the LUMC • 1MEMO_20260720

Automated isolation, IsletPrep, and Visipaque-ViaSpan: the road to the LUMC's Clinical Islet Laboratory

by Michel van der Burg, Monday 20 July 2026

Synopsis

The LUMC Clinical Islet Transplant project’s 2000 series of human islet isolations marked the transition from manual to automated pancreatic digestion using the Ricordi method. This shift prompted the drafting of our core SOPs and the training of the required isolation team.
Islets purified with “IsletPrep” — a reformulated Iodixanol-UWS solution developed with Nycomed/Axis-Shield — showed outcomes equivalent to the 1999 manual-method series: high purity, no islet loss, and preserved integrity. As GMP production of IsletPrep would not be ready in time for the planned start of work in the GMP Facility, we validated a simpler alternative combining clinical-grade Visipaque and ViaSpan, which matched IsletPrep’s results in both human and porcine islet purification. This Visipaque-ViaSpan protocol became the standard, enabling the opening of the LUMC’s Clinical Islet Laboratory (Klinisch EilandLaboratorium) in April 2001.

Citation info : 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

2000 — Pioneering Automated Islet Isolation & Clinical Grade Purification in the LUMC

Presentation : 2000 — Pioneering Automated Islet Isolation & Clinical Grade Purification in the LUMC • 1MEMO_20260720_1_Video • Michel van der Burg • TakeNode e0f677e3-689d-4697-bdad-e270eb949ee5

After the official start of the LUMC Clinical Islet Transplant Project on 22 February 1999, we began our first series of human islet isolations at the LUMC.

Our GMP facility was still under construction, so 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” (1).

That first series of human islet isolations was performed using the manual pancreas digestion method and Iodixanol-UWS purification. The results were published in December 1999, presented at the AIDSPIT Workshop in January 2000, and recently posted on this site (1,2,3).

State-of-the-Art “Automated Method”

The second series of isolations was started using the advanced “automated method” for pancreatic digestion, as developed by Camillo Ricordi — first in David Scharp’s team in Paul Lacy’s laboratory in St. Louis, and eventually in Miami with Ramon Poo of BioRep Technologies, Inc (4,5,6).

In November 1999, after setting up the custom-made equipment from BioRep Technologies in the Surgery Laboratory, I began pilot work with a few human islet isolations using the automated method, to gain hands-on experience with its elaborate set-up of equipment.

Automated Islet Isolation , LUMC 2001 • 1MEMO_20260720_1_1 • Michel van der Burg • Infographic diagram of Automated Islet Isolation setup 2001 in the LUMC, based on image from Ricordi & Strom in Nature Reviews Immunology 2004 • TakeNode 9c80e644-543c-4d2d-9775-1073465aeefa

In this method, the pancreas sits in a steel digestion chamber together with glass beads (“knikkers”), behind a screen that allows only particles smaller than 0.5 mm to pass through. Collagenase solution (Liberase-HI in Hanks’ solution) is pumped through a heating coil, warmed to 37°C, and recirculated through the chamber, progressively breaking the gland down into its component pieces. After around 30 minutes, once most islets are free, recirculation and heating are stopped, and over the following 30 minutes a room-temperature Hanks’ solution (HBSS) is pumped through the chamber while the digest leaving it is collected — then held in cold UWS for 60 minutes on ice ahead of purification.

That experience allowed me to start writing our core SOPs (Standard Operating Procedures) — the step-by-step instructions on islet isolation and related procedures required to establish the islet bank in the GMP Facility of the LUMC, in what was then still a virtually unexplored, rapidly evolving field: translating cell research into Good Manufacturing Practice (GMP)-compliant cell therapy for patients.

Islet Isolation Team

Next, the islet isolation team was built. At least two professionals are needed to perform islet isolation with the Ricordi automated method in an experimental setting; in a GMP facility, a team of three qualified professionals — sterile and non-sterile operators, plus a data recorder — is typically required.

In April 2000, having finished the core SOPs, I began training the islet isolation team — transplantation research colleagues and students — on the new islet procedures and the use of SOPs that would soon be required in the GMP Facility.

Pre-Commercial IsletPrep Trial

In July 2000, this series of islet isolations with the automated method began with our Surgery islet isolation team, now using “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” (7).

Our original, standard protocol for preparing the Iodixanol-UWS density gradients used a Working Optiprep Solution (WOP) containing 30% (w/v) iodixanol in UWS, produced by mixing OptiPrep (60% w/v iodixanol in water) with an equal volume of double-strength UWS (UWS2x). That protocol was shared with other islet centers in 1997 and has been published in OptiPrep Application sheets since 1998 (7).

I was collaborating with OptiPrep Product Manager Bjørn Henriksen (Nycomed / Axis-Shield, Oslo, Norway) to explore modifications of our Iodixanol-UWS purification solution — avoiding the need for in-house production of double-strength UWS — to facilitate its implementation in clinical human islet transplantation, both in our center and at other islet centers worldwide.

The plan was to bring the Iodixanol-UWS density solution into commercial production as a GMP-certified, ready-made product coined “IsletPrep” — the WOP mixture of equal volumes of double-strength UWS (UWS2x) and OptiPrep, in 200 ml bottles, first produced as a small batch in the Pilot Plant of Nycomed / Axis-Shield. To facilitate pharmaceutical pilot production, I modified the formulation of UWS2x by: (i) leaving out components not required for the density solution (allopurinol, glutathione, and adenosine); (ii) replacing the proprietary Pentastarch with the hydroxyethyl starch supplied by Bjørn Henriksen (HES 200, Serum-Werk, Bernburg) for use in the commercial solution; and (iii) determining the amount of solid KOH (pellets) required to obtain the desired pH of 7.4 without the need for adjustment during preparation.

The IsletPrep solution was prepared in our LUMC laboratory that same month, July 2000, for purification using the modified Iodixanol-UWS gradients in the new series of automated islet isolations with our Surgery islet team.

That work is presented in the accompanying slideshow, with a PDF available below (9).

Donor pancreases for this series (marginal organs rejected for transplantation) were procured from multiorgan donors aged 15–68 years and cold-preserved with UWS for 4–18 hours before digestion.

Islet isolation outcomes with the automated method were similar to those in our previous series (1999) using the manual method and UWS for isolation.

IsletPrep purification outcomes likewise did not differ from the results using our standard Iodixanol-UWS gradients in the 1999 series: similarly high purity, no loss of islets, and preservation of islet integrity.

Against the digest (1412 ± 291 IEQs/g; 33 ± 5% mantle-islets; 157 ± 11 µm diameter), IsletPrep purification yielded 1251 ± 181 IEQs/g — a 106% recovery — 37 ± 14% mantle-islets, 202 ± 15 µm diameter, and 74 ± 5% purity, under the mild hyperosmotic conditions (~380 mOsm) and low endotoxin content characteristic of the IsletPrep gradient.

The innovative method we introduced — first performing a test purification during islet isolation on a fraction of the digested pancreatic tissue (digest), to predict the best density solution for a simple method of islet purification in centrifuge tubes — proved to be a good alternative to the more complex method of purification in conventional continuous gradients in the Cobe centrifuge.
In practice, a 5% aliquot of the digest was distributed across four to seven small tubes, each mixed with IsletPrep to form the bottom of a one-step gradient at densities ranging from 1075 to 1090 (optional 1072, or 1100) and topped with UWS; analysing the resulting interfaces and pellets after centrifugation predicted the optimal density for bulk purification, which averaged around 1090 g/L across our isolations. For bulk purification, the digest — in 200–450 ml UWS — was mixed with IsletPrep, distributed across 10–20 conical tubes, topped with UWS, and spun for 5 minutes at 500 g, 4°C, with purified islets collected from the interface.

After the successful pre-commercial test of IsletPrep, its full production seemed only a matter of time.

Visipaque-Viaspan Purification

By the end of 2000, our isolation team had gained sufficient experience with the automated method to transition to GMP-compliant production of islets in our new lab in the LUMC GMP Facility. However, GMP production of IsletPrep itself could not be arranged immediately.

Purification without IsletPrep — that is, without the double-strength UWS component — also seemed an option: simply mixing OptiPrep and UWS had already proven sufficient for purification in animal experimental work in 1998 (7), indicating that double-strength UWS (i.e. IsletPrep) might not be strictly necessary for our Iodixanol-UWS gradients.

OptiPrep was a research-grade solution of 60% iodixanol, but could be replaced by the clinical-grade Visipaque solution of 65% iodixanol. Simply mixing Visipaque (iodixanol) and ViaSpan (UWS) — both commercial, cGMP-certified solutions — would be an elegant alternative for our Iodixanol-UWS gradients.

Test Purification Set Visipaque , LUMC 2001 • 1MEMO_20260720_1_5 • Michel van der Burg • TakeNode c79006b7-4752-4e49-9248-bdb134aa2fbc

During the first months of 2001, the 2000 series of human islet isolations was completed in our research laboratory with a successful pilot of islet purification using Visipaque-ViaSpan, again demonstrating no loss of islets, preserved islet integrity, and purity above 70%. Test purification — following the same density-prediction approach used for IsletPrep — pointed to an optimal gradient density of ≤1085 in Visipaque-ViaSpan. Against the digest (1437 ± 15 IEQs/g; 18 ± 13% mantle-islets; 185 ± 16 µm diameter), bulk purification of the full batch with Visipaque-ViaSpan yielded 1681 ± 55 IEQs/g — a 118% recovery — 13 ± 3% mantle-islets, 184 ± 8 µm diameter, and 71 ± 16% purity, under mild hyperosmotic conditions (~315 mOsm, calculated) and a low endotoxin content.

Bulk Purification Visipaque , LUMC 2001 • 1MEMO_20260720_1_6 • Michel van der Burg • TakeNode d0ea62a3-580a-429a-a45d-6d912de4d2cd

Parallel pilot animal research in early 2001 also demonstrated that Visipaque-ViaSpan purification of porcine islets yielded the same recovery and purity as the standard OptiPrep-UWS gradient based on UWS2x — as had first been found in 1998, with the similar OptiPrep-ViaSpan purification solution (7).

With these good results, Visipaque-ViaSpan was adopted as the Standard Operating Procedure.

Opening Clinical Islet Laboratory — “Klinisch EilandLaboratorium”

With the Surgery islet team, the state-of-the-art islet isolation procedure, excellent purification results, and the Visipaque-ViaSpan SOP completing our GMP documentation (8), the following month — April 2001 — our “Klinisch EilandLaboratorium” (“Clinical Islet Laboratory”) was opened for GMP-compliant production and storage of islets, in what would become known as the Dutch “islet bank” at the LUMC…to be continued…

Notes

1) 1999 — Pioneering the LUMC Clinical Islet Transplant Project • 1MEMO_20260705 • Michel van der Burg • Miracles•Media • URL (1) michelvanderburg.com/2026/07/05 • URL (2) https://1memo.substack.com/p/1999-pioneering-the-lumc-clinical

2) Van der Burg MPM, Ringers J, Baranski A, Bouwman E, Terpstra OT. No loss of human (mantle-) islets by OptiPrep-UWS purification following isolation in UWS (Abstract). Acta Diabetol 36, 230 (1999). URL https://doi.org/10.1007/s005920050168 . PMID: 10664329 . Abstract available online (1).

3) Van der Burg MPM, Ringers J, Baranski A, Bouwman E, Terpstra OT. No loss of human (mantle-) islets by OptiPrep-UWS purification following isolation in UWS. 19th AIDSPIT Workshop of the European Association for the Study of Diabetes (EASD) in Igls (Austria) Jan 23–25, 2000. Oral presentation slideshow available online (1).

4) Piemonti L, Pileggi A. 25 YEARS OF THE RICORDI AUTOMATED METHOD FOR ISLET ISOLATION. CellR4 Repair Replace Regen Reprogram. 2013;1(1):8-22. PMID: 30505878; PMCID: PMC6267808. URL (1) https://www.cellr4.org/wp-content/uploads/sites/2/2013/06/Article-2013-1-e128.pdf URL (2) https://pmc.ncbi.nlm.nih.gov/articles/PMC6267808/

5) Who we are. Biorep. URL https://biorep.com/who-we-are/

6) Scharp DW, Arulmoli J, Morgan K, Sunshine H, Hao E. Advances in Human Islet Processing: Manufacturing Steps to Achieve Predictable Islet Outcomes from Research Pancreases. OBM Transplantation 2019; 3(1): 052; doi:10.21926/obm.transplant.1901052. URL https://www.lidsen.com/journals/transplantation/transplantation-03-01-052

7) Islet purification from bench to bedside • @1MEMO_20260623 • Michel van der Burg • Miracles.Media • URL michelvanderburg.com/2026/06/23/

8) IsletPrep based standard operating procedures (SOPs) were submitted for review with the 1st edition of the GMP Documentation for the LUMC Clinical Islet Laboratory (29 November 2000). The IsletPrep based SOPs were replaced with Visipaque-Viaspan based SOPs in the 1st edition (2001) GMP Documentation of the LUMC Clinical Islet Laboratory (KEL). Illustrated in presentation (9).

9) Presentation : 2000 — Pioneering Automated Islet Isolation & Clinical Grade Purification in the LUMC • 1MEMO_20260720_1 • Michel van der Burg • Miracles•Media • Automated isolation, IsletPrep, and Visipaque-ViaSpan: the road to the LUMC’s Clinical Islet Laboratory by Michel van der Burg • URL michelvanderburg.com/2026/07/20 • Video (1MEMO_20260720_1_Video) • Poster (1MEMO_20260720_1_Poster) • Handout (1MEMO_20260720_1_Handout)

1MEMO_20260720_1_Handout Download

Presentation : 2000 — Pioneering Automated Islet Isolation & Clinical Grade Purification in the LUMC • 1MEMO_20260720_1_Handout • Michel van der Burg • TakeNode ddda9083-ca1e-4b00-b29d-b1377a0f050e

Images (License TakeNode)

Presentation : 2000 — Pioneering Automated Islet Isolation & Clinical Grade Purification in the LUMC • 1MEMO_20260720_1_Poster • Michel van der Burg • TakeNode 42097357-1944-456b-b3a7-ce81ba03903b

Automated Islet Isolation , LUMC 2001 • 1MEMO_20260720_1_1 • Michel van der Burg • Infographic diagram of Automated Islet Isolation setup 2001 in the LUMC, based on image from Ricordi & Strom in Nature Reviews Immunology 2004 • TakeNode 9c80e644-543c-4d2d-9775-1073465aeefa

IsletPrep-UWS , LUMC 2000 • 1MEMO_20260720_1_2 • Michel van der Burg • TakeNode 03a466fd-fa84-4044-a9ca-06116b5fb1ca

Test Purification Set IsletPrep , LUMC 2000 • 1MEMO_20260720_1_3 • Michel van der Burg • TakeNode 75bc6084-f93d-4e02-acbc-a541fb9b7233

Bulk Purification IsletPrep , LUMC 2000 • 1MEMO_20260720_1_4 • Michel van der Burg • TakeNode 09726d07-8cd5-44f2-a412-32f524f4825f

Test Purification Set Visipaque , LUMC 2001 • 1MEMO_20260720_1_5 • Michel van der Burg • TakeNode c79006b7-4752-4e49-9248-bdb134aa2fbc

Bulk Purification Visipaque , LUMC 2001 • 1MEMO_20260720_1_6 • Michel van der Burg • TakeNode d0ea62a3-580a-429a-a45d-6d912de4d2cd

Visipaque-ViaSpan SOPs • 1MEMO_20260720_1_7 • Michel van der Burg • Illustration of “Procedure report” pages on using Visipaque for “Test tubes” preparation (right) and “Purification” (middle) during human islet isolation, with the pancreatic digest in UWS (ViaSpan), from the 2001 standard operating procedures — the SOPs, now “Obsolete” (i.e. outdated) — from the GMP documentation for the Clinical Islet Laboratory (Klinisch Eilandlaboratorium) at LUMC (Leiden, Netherlands). Translated from Dutch by the author, Michel van der Burg • TakeNode 66f5207b-db1a-4166-bc22-0104ec509449

Acknowledgements — I thank Bjørn Henriksen (International Product Group Manager Density Gradient Media Nycomed / Axis-Shield PoC AS (Oslo, Norway) for our collaboration on our iodixanol and IsletPrep work ; Camillo Ricordi (Director of the Diabetes Research Institute, Miami) and Ramon Poo (BioRep Technologies, Miami) for their help in setting up automated islet isolation in our lab ; Amon Wafelman (deputy head of the Interdivisional GMP-Facility, Department of Clinical Pharmacy and Toxicology, LUMC) for collaboration on our SOPs and GMP setup of 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, 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’.

This work was shared previously with the other islets centers, in personal communication in 2001 — in detail with Jonathan Lakey (Edmonton, Canada), and in summary with Daniel Brandhorst (Giessen, Germany), José Oberholzer (Geneva, Switzerland) — and with Sue Swift (Leicester, UK) in 2003.

#IsletPrep #UWS2x #islets #islet #Langerhans #isolation #automated #purification #isletbank #surgery #clinical #laboratory #launch #GMP #cleanroom #facility #Surgery #KEL #CITX #LUMC #Holland #Netherlands #Leiden #hospital #Eurotransplant #human #donor #Visipaque #optiprep #iodixanol #ViaSpan #UWS #density #gradient #pancreas #UW #university #Wisconsin #transplantation #diabetes #history #research #memoir #1memo #michelvanderburg #BioRep #CamilloRicordi #DRI #Miami #Nycomed #Axis #Klinisch #Eilandlaboratorium

1999 — Pioneering the LUMC Clinical Islet Transplant Project • 1MEMO_20260705

by Michel van der Burg , Sunday 5 July 2026 , Updated 10 July 2026

Abstract

In 1997, Onno Terpstra, Head of Surgery at Leiden University Medical Center (LUMC), asked Michel van der Burg to develop a plan for a clinical islet isolation and transplantation program. Following a working visit to the Diabetes Research Institute in Miami in spring 1998, where the Iodixanol-UWS purification method was tested on human islets, van der Burg began the islet isolation program at LUMC and the setting up of the Clinical Islet Laboratory (Klinisch Eilandlaboratorium, KEL) within a new GMP facility at LUMC, in collaboration with Amon Wafelman, executive head of the GMP facility. A business plan was submitted to the LUMC Board of Directors in November 1998 and approved on February 22, 1999, formally launching the project. The first series of human islet isolations, using manual pancreas digestion and Iodixanol-UWS purification, began in March 1999. The results were published in December 1999 and presented at the AIDSPIT Workshop in January 2000. From 2000 onward, the laboratory adopted the automated Ricordi method, using equipment supplied through BioRep Technologies in Miami.

Citation info : 1999 — Pioneering the LUMC Clinical Islet Transplant Project • 1MEMO_20260705 • Michel van der Burg • Miracles•Media • URL michelvanderburg.com/2026/07/05

1999 — No Loss of Human Islets in LUMC • 1MEMO_20260705_4_0 • Michel van der Burg • Miracles•Media • TakeNode 28097648-0b1d-4c1e-94cc-52e57738f04a • Presentation of the outcome of the first series of human islet isolation performed in 1999 in the Leiden University Medical Center (LUMC).

The LUMC clinical islet transplantation project began in 1997 on the initiative of the Department of Surgery at the LUMC, where I had been conducting animal-experimental research within the Transplantation Section since 1981 — first into the optimal method for pancreas transplantation, and subsequently into the transplantation of islets of Langerhans following isolation and purification of the islets from the pancreas (1-11).

Following successful animal-experimental islet transplantation, and a brief period of experimental human islet isolation in the early 1990s (8,9), Onno Terpstra, the head of our Surgery Department, asked me in the summer of 1997 to explore our options for starting clinical islet isolation and transplantation at our center — the Leiden University Medical Center (LUMC) — and to prepare a roadmap.

After first gaining experience in the spring of 1998 with the human islet transplant program in Miami — during which, in the course of isolating human islets of Langerhans, our new islet purification method also proved successful (11,12) — I was able to begin actually setting up the human islet project in Leiden in the summer of 1998.

Our innovative procedure for purifying islets in Iodixanol-UWS was further developed and published that summer of 1998 in collaboration with Nycomed (10).

The LUMC had recently begun renovating a wing of the building to establish a GMP facility with six so-called cleanrooms, intended to guarantee maximum protection and quality in the manufacture of medicinal products. After the summer of 1998, I was just in time to join those renovation plans, working together with Amon Wafelman — the executive head of the future GMP facility — to realize the necessary modifications in the GMP wing, with one of the six cleanrooms specially fitted out for use as our clinical islet laboratory. Although the cleanrooms had not originally been intended for permanent use, round-the-clock use of a cleanroom for the islet project could nonetheless become an option, with support from the Board of Directors.

By November 1998, I had incorporated a plan for setting up the Clinical Islet Laboratory (KEL) — and for the first 20 islet isolation procedures — into a business plan presented on behalf of our Department of Surgery to the LUMC Board of Directors (13; 1MEMO_20260705_1).

Business Plan CITX • 1MEMO_20260705_1_Front • Michel van der Burg • Miracles•Media • TakeNode 84c8fbb7-1e21-4e63-8940-3a79db30a0fa • Business plan Clinical Islet Transplantation Project (CITX) prepared November 3, 1998 for the Board of Directors of the LUMC . Front page image of the PDF file in Notes (13; 1MEMO_20260705_1) .

On February 22, 1999, the LUMC Executive Board approved the plan and authorized the necessary material resources, officially launching the islet transplantation project — as announced that month in the LUMC magazine ‘Cicero’ (14; 1MEMO_20260705_2).

‘The Transplantation of Islets of Langerhans: A Leiden First’, a pull quote from the feature story “Ernstiger ziek en wèl genezen” by Evert Pronk, in the LUMC news magazine Cicero, 5 February 1999 (ISSN 0920-2900) • 1MEMO_20260705_2

Quote (my translation):

“The Transplantation of Islets of Langerhans: A Leiden First

… The isolation of islets will take place at the LUMC. What remains is the completion of the GMP facility (Good Manufacturing Practice), the laboratory whose quality standards are so stringent that “products” can be manufactured that are suitable for administration to humans …”

The project was registered with the Eurotransplant organization for the allocation of donor organs — marginal donor organs, i.e. not suitable for clinical transplantation — to start up the islet isolation procedure, without transplantation being the aim at that stage.

In March 1999, we received the first donor organs via Eurotransplant for an initial experimental series of islet isolations. With the approval of the Board of Directors — since the GMP facility was still under construction — work could already begin in the Surgery Laboratory, gaining hands-on experience with human islet isolation, the donor procedure, islet culture, and all other facets of operating an “islet bank.”

Help for diabetic glands • April 1999 News Volkskrant • 1MEMO_20260705_3 • Miracles•Media • TakeNode ccbd39ce-9498-4bc9-aefb-96ae6f9e5791 • Help for diabetic glands (dutch: Hulp voor suikerzieke klieren) in Dutch national newspaper De Volkskrant , 10 April 1999 , by John Ekkelboom

In April 1999, the Dutch national newspaper ‘De Volkskrant’ announced the LUMC project in the article “Help for diabetic glands” (“Hulp voor suikerzieke klieren”) by John Ekkelboom (15; 1MEMO_20260705_3), with contributions from Jan Ringers (Head of the Transplantation Section of our department) and myself.
Excerpts (translated from Dutch):

“Help for diabetic glands

Some patients with juvenile diabetes may benefit from a transplantation of islets of Langerhans. Cells from these islets replenish the insulin deficiency. The Leiden University Medical Center (LUMC) will soon treat several patients with this new method.

… Dr. Jan Ringers, a transplant surgeon at the LUMC, says that the chance of success has increased to such an extent that his hospital now also considers the procedure justifiable …

… Dr. Michel van der Burg attributes the fact that this scenario did not go as well abroad in the early years to, among other things, less suitable enzymes and the premature insertion of the transplant. As a scientific researcher at the LUMC, he focuses on the isolation of the islets …”

— John Ekkelboom, April 10, 1999, Volkskrant

First series of human islet isolations in Leiden

In March 1999, the first series of human islet isolations began in the LUMC Surgery Laboratory, applying the manual method of donor pancreas digestion, with purification of the islets in the new Iodixanol-UWS gradients.

Human islets of Langerhans prepared by purification in the Iodixanol-UWS solution by Michel van der Burg at the start of the LUMC islet transplant project, March 1999, Leiden University Medical Center (LUMC), Leiden, Holland • 1MEMO_20260623_1 • Michel van der Burg • Miracles•Media • TakeNode 30b1f224-f963-480e-838e-42b4f8dfa559

This Iodixanol-UWS purification method had been developed in our animal-experimental research on the isolation and purification of porcine islets for successful transplantations, first in diabetic mice, then in rats and monkeys (7,16).

The Iodixanol-UWS purification method had also proved promising the previous year in my pilot research during human islet isolations at the Diabetes Research Institute in Miami, where the purified human islets were successfully transplanted into nude mice (11).

The results of our first series of human islet isolations at the LUMC in 1999 were published in December 1999 and subsequently presented at the 19th AIDSPIT Workshop of the European Association for the Study of Diabetes (EASD) in Igls, Austria, in January 2000 (17,18,19,20; 1MEMO_20260705_4).

No Loss of Human Islets • AIDSPIT 2000 • 1MEMO_20260705_4 • Michel van der Burg • Miracles•Media • Outcome 1st series in 1999 of human islet isolation in LUMC presented at the 19th AIDSPIT Workshop of the European Association for the Study of Diabetes (EASD) in Igls, Austria, January 23–25, 2000 . Details , plus handout and abstract for download in Notes (17,18,19,20).

State of the Art — Ricordi Method & BioRep Technologies

Work then began on the second series of isolations, this time using the state-of-the-art “Ricordi Automated Method” for pancreas digestion (21), as further developed by Camillo Ricordi, first in David Scharp’s team in Paul Lacy’s laboratory in St. Louis (USA) and eventually in Miami together with Ramon Poo of BioRep Technologies, Inc.

In setting up the state-of-the-art procedure for islet isolation from the pancreas using the Ricordi Automated Method at the LUMC, I worked at the end of 1998 together with Gerard Verschagen, head of the precision mechanics workshop of the Laboratory of Physiology of the LUMC (22), on developing a compressed-air-driven shaking device for the Ricordi chamber, for which modifications to the GMP complex were also planned.

Earlier in 1998, during my working visit to the Diabetes Research Institute in Miami, I had met Mr. Ramon Poo, who — alongside his day job as a designer and manufacturer of plastic bottles in Miami (Altira, Inc.) — also contributed on a voluntary basis to Ricordi’s islet project in Miami. Through his firm founded specifically for this purpose, BioRep Technologies, Inc., Poo designed and manufactured the special equipment for the Ricordi isolation method, including the digestion chamber and a shaking device for the Ricordi chamber (23,24). During that working visit, Mr. Poo also gave me a stainless-steel Ricordi chamber and other components for the “Ricordi setup” to start up the procedure in our laboratory in Leiden, Holland, in the LUMC.

During discussions at the end of 1998, by phone and fax, with Mr. Poo about our design in Leiden of the shaking device based on the BioRep model, it emerged that BioRep could supply us with a new model of shaking device — the Wrist Shaker, a model not yet patented — with the permission of Camillo Ricordi’s team, on condition of “no disclosure.”

From 1999 onward, the Wrist Shaker (Model No. B-3-G) and other BioRep equipment were imported, after which, from 2000 onward, the Ricordi Automated Method for pancreas digestion was applied for islet isolation at the LUMC…to be continued…

Notes

1) Pancreatic islet transplantation Thesis Repository Leiden University • 20221125 • Michel van der Burg • Miracles•Media • . Persistent URL https://hdl.handle.net/1887/3486604

2) Leiden Islet Laboratory History • 20240803 • Michel van der Burg • michelvanderburg•com • URL https://michelvanderburg.com/2024/08/03/leiden-islet-laboratory-history-20240803/

3) Pancreas & Islet Transplantation Program • 20240912 • Michel van der Burg • michelvanderburg•com • URL https://michelvanderburg.com/2024/09/12/pancreas-islet-transplantation-program-20240912/

4) Pancreatic Islet Isolation With UW Solution • A New Concept • Michel van der Burg • Miracles.Media • @1MEMO 20241224 • URL michelvanderburg.com/2024/12/24/

5) Percoll UWS Purification Pancreatic Islets • ESOT 1991 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20250114 • URL michelvanderburg.com/2025/01/14/

6) Islet Transplantation Breakthrough in Leiden University Hospital • 20240830 • Michel van der Burg • michelvanderburg•com URL https://michelvanderburg.com/2024/08/30/islet-transplantation-breakthrough-in-leiden-university-hospital-20240830/

7) Successful Islet Transplantation After Purification in Iodixanol-UWS • IPITA 1999 Sydney • @1MEMO 20260326 • Michel van der Burg • Miracles.Media • URL michelvanderburg.com/2026/03/26/

8) 1989 — First series of human islet isolations in Leiden. In 1989-1990 we performed a first series of islet isolations from human donor pancreases using our novel techniques of isolation and purification in UW organ preservation solution – in association with a European Concerted Action for the Treatment of Diabetes – the Brussels headed (Daniel Pipeleers) ‘Multicenter program on the treatment of diabetes by islet cell transplantation’.

9) Pittsburgh 1992 Cell Transplant Society • 20240812 • Michel van der Burg • michelvanderburg•com • URL https://michelvanderburg.com/2024/08/12/pittsburgh-1992-cell-transplant-society-20240812/

10) Islet purification from bench to bedside • @1MEMO_20260623 • Michel van der Burg • Miracles.Media • URL michelvanderburg.com/2026/06/23/

11) Efficacy of the novel iodixanol-UWS density gradient for human islet purification • Igls Aidspit 1999 • Michel van der Burg • Miracles.Media • 20241202 • URL michelvanderburg.com/2024/12/02/

12) Human Islet Isolation • DRI Miami 1998 • Michel van der Burg • Miracles.Media • @1MEMO 20250204 • URL michelvanderburg.com/2025/02/04/

13) Business Plan CITX • 1MEMO_20260705_1 • Michel van der Burg • Miracles•Media • TakeNode 62317860-28ff-46a6-9e2b-20910f7f4aa6 • Business plan Clinical Islet Transplantation Project (CITX) prepared November 3, 1998 for the Board of Directors of the LUMC (English translation by author). PDF for viewing and download below 1MEMO_20260705_1.

1MEMO_20260705_1 Download

14) A Leiden First • 1MEMO_20260705_2 • Miracles•Media • TakeNode d3d3effe-ee4c-479c-8051-c78a90746eb1 • “The Transplantation of Islets of Langerhans : A Leiden First “. Pull quote from the feature story ‘Ernstiger ziek en wèl genezen’ by Evert Pronk, in the LUMC news magazine Cicero, 5 February 1999 (ISSN 0920-2900) .

15) Help for diabetic glands • April 1999 News Volkskrant • 1MEMO_20260705_3 • Miracles•Media • TakeNode ccbd39ce-9498-4bc9-aefb-96ae6f9e5791 • Help for diabetic glands (dutch: Hulp voor suikerzieke klieren) in Dutch national newspaper De Volkskrant , 10 April 1999 , by John Ekkelboom . Text (only) online in Volkskrant archive URL https://www.volkskrant.nl/wetenschap/hulp-voor-suikerzieke-klieren~b7046616/

16) Primate Islet Isolation and Purification in Iodixanol-UWS • @1MEMO_20260425 • Michel van der Burg • Miracles.Media • URL michelvanderburg.com/2026/04/25/

17) Van der Burg MPM, Ringers J, Baranski A, Bouwman E, Terpstra OT. No loss of human (mantle-) islets by OptiPrep-UWS purification following isolation in UWS. 19th AIDSPIT Workshop of the European Association for the Study of Diabetes (EASD) in Igls (Austria) Jan 23–25, 2000 . Abstract (Page 230) in : Acta Diabetol 36, 205–231 (1999). https://doi.org/10.1007/s005920050168 . PMID: 10664329

18) No Loss of Human Islets • AIDSPIT 2000 • 1MEMO_20260705_4 • Michel van der Burg • Miracles•Media • Video of slideshow TakeNode bb4091a1-374f-4a04-86a1-67e371074109 • URL https://youtu.be/txSFax_nR2I

19) Ibid. Handout of slideshow : 1MEMO_20260705_4_PDF • Michel van der Burg • Miracles•Media • TakeNode 35766a9b-d1b1-47af-9371-4edca9c3ad0d • Download PDF below ( 1MEMO_20260705_4_PDF )

1MEMO_20260705_4_PDF Download

20) Van der Burg MPM, Ringers J, Baranski A, Bouwman E, Terpstra OT. No loss of human (mantle-) islets by OptiPrep-UWS purification following isolation in UWS (Abstract). Acta Diabetol 36, 230 (1999). URL https://doi.org/10.1007/s005920050168 . PMID: 10664329

Ibid. Abstract copy : 1MEMO_20260705_4_PMID_10664329 • Michel van der Burg • Miracles•Media • TakeNode fa10d5e9-3df9-46e0-b8cf-7f9f9f853526 • Download PDF below ( 1MEMO_20260705_4_PMID_10664329 )

1MEMO_20260705_4_PMID_10664329 Download

21) Piemonti L, Pileggi A. 25 YEARS OF THE RICORDI AUTOMATED METHOD FOR ISLET ISOLATION. CellR4 Repair Replace Regen Reprogram. 2013;1(1):e128. PMID: 30505878; PMCID: PMC6267808. URL https://pmc.ncbi.nlm.nih.gov/articles/PMC6267808/

22) Leiden Islet Isolation Chamber • Michel van der Burg • Miracles.Media • @1MEMO 20250116 • URL michelvanderburg.com/2025/01/16/

23) How a Family Business Has Buoyed the Diabetes Research Institute (DRI) URL https://www.mwhoskinsmedia.com/2019/12/how-family-business-has-buoyed-diabetes.html

24) Who we are. Biorep. URL https://biorep.com/who-we-are/

#islets #islet #Langerhans #isolation #purification #isletbank #first #launch #Cicero #Volkskrant #newspaper #news #GMP #cleanroom #facility #Surgery #KEL #CITX #LUMC #Holland #Netherlands #Leiden #hospital #Eurotransplant #human #donor #surgery #clinical #laboratory #optiprep #iodixanol #ViaSpan #density #gradient #UWS #pancreas #UW #university #Wisconsin #transplantation #diabetes #man #history #research #history #memoir #1memo #michelvanderburg #BioRep #CamilloRicordi #DRI #Miami #Nycomed #Visipaque

Citation info : 1999 — Pioneering the LUMC Clinical Islet Transplant Project • 1MEMO_20260705 • Michel van der Burg • Miracles•Media • URL michelvanderburg.com/2026/07/05

Human Islet Isolation • DRI Miami 1998 • @1MEMO 20250204

Summer 1997, Onno Terpstra, the head of our Surgery Department, asked me to explore our options for starting clinical islet isolation and transplantation in our center – the Leiden University Medical Center (LUMC), and prepare a roadmap.

September 1997, at the IPITA congress in Milan (1) , I learned from Camillo Ricordi, the scientific director of the Diabetes Research Institute (DRI) in Miami – where many guest collaborators work – that visiting the DRI some weeks might be a good option to gain sufficient first work experience in his clinical islet transplantation group.

December 1997, with a ‘Roadmap’, I got the green light to start the operationalization of clinical islet transplantation in the LUMC, first with a working visit to Miami to study the state of the art ‘Ricordi’ method of human islet isolation, and then start the human islet isolation work in our Surgery lab in Leiden.

In 1990 I had already gained some initial research experience in our Leiden Islet Laboratory with a small number of isolations of islets from human donor organs, using our innovative method of density gradient purification based on the UW solution (2).

During the first three months of 1998 I worked intensively with my student colleague Josephine Rijkelijkhuizen so that she would be able to continue our xenotransplantation research project as independently as possible in our Surgery research team.

April 1998, after participating in the 1st Workshop on Clinical Islet Transplantation in New Orleans (3) – the ideal introduction – a fruitful working visit to the DRI in Miami followed (4,5), with intensive collaboration with the DRI team on, among other things, six human islet isolations, and also the simultaneously (parallel) conducted research into the purification of the human islets in our Iodixanol gradient in UW-Solution (6).

Here a slideshow illustrating this team up with the DRI team in Miami , working on human islet isolation and purification in the innovative Iodixanol-UWS gradient, April-May 1998.

Notes

1) Innovative Islet Purification in Iodixanol-UWS • IPITA 97 • Michel van der Burg • Miracles.Media • @1MEMO 20250128 • TakeNode • URL michelvanderburg.com/2025/01/28/

2) Percoll UWS Purification Pancreatic Islets • ESOT 1991 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20250114 • URL michelvanderburg.com/2025/01/14/

3) Invited participant 1st Workshop on Clinical Islet Transplantation, New Orleans (LA, USA) April 17–19, 1998

4) Working visit April – May 1998 at the “fast track” center of the Diabetes Research Institute (Scientific director Prof. C. Ricordi, MD) of the University of Miami (Miami, FL, USA)

5) DRI Dream Team • Michel van der Burg • Miracles.Media • @1MEMO 20250105 • URL michelvanderburg.com/2025/01/05/

6) Human Islet Purification Miami 1998 • Michel van der Burg • Miracles.Media • 20181102 • URL michelvanderburg.com/2018/11/02/

Citation info : Human Islet Isolation • DRI Miami 1998 • Michel van der Burg • Miracles.Media • @1MEMO 20250204 • TakeNode 86e4a319-a769-44d5-8fa5-de2ca90ab63c • URL michelvanderburg.com/2025/02/04/

Optiprep For Human Islet Purification • Cell Transplant Society 1999 • @1MEMO 20250203

Optiprep For Human Islet Purification • Cell Transplant Society 1999 • Michel van der Burg • Miracles.Media • @1MEMO 20250203 • TakeNode bad757b8-674c-4371-938c-ac73287bc457

Poster (#57) presentation Michel van der Burg, Cell Transplant Society congress 1999 in Montreux, Switzerland (1,2)

Outcome of the first series of human islet purifications with the novel Iodixanol -UWS density gradient — developed in the Leiden Islet Laboratory of the LUMC — performed during my working visit April – May 1998 at the “fast track” center of the Diabetes Research Institute (Scientific director Prof. C. Ricordi, MD) of the University of Miami (Miami, FL, USA).

Notes

1) Van der Burg MPM, Ranuncoli A, Molano R, Kirlew T, Ringers J, Bouwman E, Terpstra OT, Ricordi C. Optiprep for human islet purification. 4th International congress of the Cell Transplant Society, Montreux (Switzerland) March 21–24, 1999 .

2) Van der Burg MPM, Ranuncoli A, Molano R, Kirlew T, Ringers J, Bouwman E, Terpstra OT, Ricordi C. Optiprep for human islet purification (Abstract). Cell Transplant 1999; 8: 184. Download abstract below 1MEMO_20250202_3

1MEMO_20250202_3🔗Download

Citation info : Optiprep For Human Islet Purification • Cell Transplant Society 1999 • Michel van der Burg • Miracles.Media • @1MEMO 20250203 • URL michelvanderburg.com/2025/02/03/

DRI Dream Team • @1MEMO 20250105

DRI Dream Team • Miami 1998 • Michel van der Burg • Miracles.Media • 20250105_1 • TakeNode e6258505-55a8-4365-bb70-7a1dcd7b5426

Team up with researchers at the Diabetes Research Institute in Miami , working on human islet transplantation (1).

“For National Geographic…” announced Camillo Ricordi for fun, that Monday , April 27th in 1998 at the Diabetes Research Institute, when the DRI islet isolation team posed in GMP outfit for this picture (2) — with Elina Linetsky on the left , and me standing second from right — taken after finishing our human islet isolation work, including islet purification in the iodixanol gradient in UW-Solution (3).

Notes

1) Working visit April – May 1998 at the “fast track” center of the Diabetes Research Institute (Scientific director Prof. C. Ricordi, MD) of the University of Miami (Miami, FL, USA)

2) Blown up image (from small GIF online in the early DRInet days), taken through a reflecting window.

3) Human Islet Purification Miami 1998 • Michel van der Burg • Miracles.Media • 20181102 • URL michelvanderburg.com/2018/11/02/

Citation info : DRI Dream Team • Michel van der Burg • Miracles.Media • @1MEMO 20250105 • URL michelvanderburg.com/2025/01/05/