by Michel van der Burg , June 23rd, 2026

Abstract

Michel van der Burg developed the Iodixanol-UWS islet purification method at the Leiden University Medical Center, starting with UWS-based density gradients in 1989, switching to Iodixanol-UWS after a 1995 meeting with Terry Ford, refining and sharing the technique with islet centers worldwide with Nycomed/Axis-Shield collaboration (1997–2001), and bringing it into clinical human islet transplantation in Leiden (1999–2002), where a simplified Visipaque-ViaSpan version became the GMP standard.

Summary

This memoir traces the development of the Iodixanol-UWS islet purification method, authored by Michel van der Burg, covering roughly 1989 to the early 2000s.

Origins (1989–1994): The story begins at Leiden University Hospital, where Van der Burg started using UW-Solution (UWS) for islet isolation in 1989 and began experimenting with UWS-based density gradients to purify islets — testing Pentastarch, Dextran, and ultimately Percoll added to UWS. Percoll-UWS became the standard method through his PhD work, completed in 1994.

The Iodixanol breakthrough (1995–1997): A chance 1995 conversation with researcher Terry Ford at an IPITA congress in Miami introduced Van der Burg to Iodixanol (marketed as Optiprep), a newer, more practical density agent than Percoll. He began designing an Iodixanol-UWS gradient, finalizing a protocol by November 1995 and adopting it in the Leiden lab in 1996 for pig islet xenotransplant research, where it dramatically improved islet yield and viability.

Spreading the method (1997–1998): After presenting results at the 1997 IPITA congress in Milan, Van der Burg fielded requests from islet centers worldwide (Geneva, Oxford, Chicago, Minneapolis, and others), sharing his protocol and helping coordinate Pentastarch supply. This led to collaboration with Nycomed (later Axis-Shield), producers of Optiprep, including biochemists Terry Ford and John Graham and product manager Bjørn Henriksen. Together they co-authored a series of published “Application Sheets” (1998–2020) detailing the method, and explored alternative formulations (iodixanol powder vs. Optiprep, with/without double-strength UWS).

Clinical translation (1999–2002): In 1999, the LUMC approved a clinical islet transplantation program, and Van der Burg’s Iodixanol-UWS gradient was used for the first human islet purifications in Leiden. Parallel efforts with Nycomed aimed to commercialize a ready-made product (“IsletPrep”). By 2001, the method was simplified further for GMP cleanroom use in Leiden, mixing clinically certified Visipaque (iodixanol) directly with ViaSpan (UWS) — the approach that became a first standard operating procedure for the Leiden clinical islet transplantation project, and was integrated recently into the automated “PRISM” technique.

Throughout, the piece blends personal recollection (meetings, letters, an enthusiastic 1997 email from Bernhard Hering) with a detailed technical and institutional history of how a laboratory innovation moved from animal models to international clinical practice.

Introduction

In order to obtain pure islets of Langerhans from the pancreas for transplantation of the islets in diabetics, a new highly successful islet purification solution was developed from 1995 using a mixture of Iodixanol in a (modified) University of Wisconsin solution, the so-called Iodixanol-UWS solution.

Using this Iodixanol-UWS solution for purification of the islets from pancreases greatly improved the outcome, showing virtually no loss of highly purified viable islets — allowing successful islet purification for transplantation, first from 1997 in our animal models (1), and next from 1998 in human islet isolation (2,3,4).

Iodixanol Encounter

My first encounter with Iodixanol (Optiprep) was June 1995 during the 5th IPITA congress in Miami, speaking with Terry Ford who had been researching Nycodenz (5), a forerunner of Iodixanol — a dimer of Nycodenz (6).
Both Nycodenz and Iodixanol (Optiprep) are nonionic iodinated density gradient agents originally developed and produced by Nycomed A/S (Oslo, Norway) — later produced by Axis-Shield and Alere Technologies.
In 1995, Iodixanol was just recently brought to the market as Optiprep, a 60% solution of iodixanol in water, by Nycomed (Oslo, Norway), and Terry Ford gave me the address for obtaining Optiprep in Holland. He co-authored a first poster presentation on the use of an iodixanol (Optiprep) in Hanks medium for juvenile pig islet purification at the 14th AIDSPIT in Igls, Austria, Jan 1995 (32).

I had completely forgotten this brief first meeting with Terry Ford in Miami in 1995, and only recently encountered a memo on this in my archives. I would start working with Terry Ford in 1998 when I was collaborating with Nycomed to explore modifications of our Iodixanol-UWS purification solution to facilitate its implementation in clinical human islet transplantation in Leiden and elsewhere in other islet centers around the world.

Following that June 1995 talk with Terry Ford, I started, in August 1995, designing our islet purification solution of Iodixanol in UW-Solution (UWS). Designing that Iodixanol-UWS for islet purification was a logical progression from our previous density gradient solutions based on the UWS, using either the UWS component Pentastarch (Pentafraction of Hydroxyethyl starch; HES), dextran, Ficoll, or Percoll.

Designing Density Gradients in UWS

Theoretically, the simplest, most elegant design for islet purification in UWS is increasing the native Pentafraction component (‘Pentastarch’) to increase the density of the solution — that is, not adding foreign elements.
That Pentastarch-UWS density gradient was actually also the first density gradient in UW-Solution that I conceived and planned for islet purification in 1989, the year we started using the UW-Solution as the islet isolation solution prior to purification in density gradients, showing consistent near-complete islet purification (7,8).

The news of the exciting finding of over 90% purity of these UWS-isolated islets was presented in a poster, September 1989, at the 2nd International Congress on Pancreatic and Islet Transplantation (IPITA) in Minneapolis, USA (8), where I further discussed Sep 20th 1989 with Robert Carter and Gerry Toole — the DuPont team supporting our work — my research plan (1MEMO_20260623_2) on using UWS also as the islet purification solution by increasing the concentration of the Pentafraction component of UWS (aka PentaStarch) — DuPont’s proprietary HES product (Hydroxyethyl starch, a nonionic starch derivative) used in the production of UWS (DCC-10323 UW Organ Preservative Solution; Du Pont Critical Care, Waukegan, USA; later known as ViaSpan).

Early 1990, while waiting for the arrival of the Pentafraction to create the planned PentaStarch-UWS gradient, I started experiments with the addition of other ‘impermeants’ for islet purification: first, March 1990, with islet purification in a Dextran-UWS density gradient; next, April 1990, in a Percoll-UWS gradient; and finally, May 1990, using the Pentastarch-UWS gradient (9).

Increasing the Pentastarch content in UWS not only increases the density of the solution, it also increases the dehydrating properties of the solution, resulting in islets with an increased density pelleting with the unwanted exocrine tissue after centrifugation, in the high-density bottom. Thus, comparing Pentafraction (Pentastarch) and other impermeants added to UWS, the best results for islet purification were obtained using Percoll in UWS, and islet purification in Percoll-UWS was the method of choice in the early 1990s for the PhD islet research I finished in November 1994 (10,11,12,13).

Introduction of Iodixanol-UWS

This solution of Iodixanol in modified UWS was a logical progression from our previous density gradients based on the UWS, such as the successful Percoll-UWS density gradient (10,11,12,13) — a similar solution of impermeants (that do not readily enter cells) with a similar osmolarity (close to that of the tissue).
The iodixanol solution is more practical, though — easier to prepare and handle — and has the important advantage that both iodixanol and the UW-solution are used clinically.
Iodixanol is clinically used as an X-ray contrast medium (Visipaque), and the University of Wisconsin (UW) solution is clinically used for donor organ preservation (ViaSpan; Belzer UW® Cold Storage Solution).

That Percoll-UWS gradient used in the early 90s was prepared using a 10-times concentrated modified (basal) UWS, which I custom-made in our laboratory (10,11,12,13).
For the new Iodixanol-UWS gradient, Optiprep was mixed with a 2-times concentrated modified (basal) UWS, also custom-made in our laboratory.

The first standard operating procedure for this Iodixanol-UWS gradient for our pig islet isolation research was completed in November 1995. In July 1996, the Iodixanol-UWS gradient was introduced in our Leiden islet laboratory (14), replacing the Percoll-UWS gradient for new large-scale pig islet xeno-transplant work. Using this Iodixanol-UWS solution for purification of the fragile islets from pig pancreases greatly improved the outcome, showing virtually no loss of the highly purified islets.

In September 1997, our results were reported in talks at the 6th Congress of the International Pancreas and Islet Transplant Association (IPITA) in Milan, Italy (15,16), where I began sharing the materials and methods of our purification procedure in detail during face-to-face meetings in Milan with colleagues from other islet centers, and subsequently, upon returning home, in response to the many requests I found in my email and fax inbox from other islet centers in, e.g., Geneva (José Oberholzer), Leicester (Heather Clayton), LA (Yoko Mullen), Oxford (Derek Gray), London (Steve Hughes), Chicago (Horacio Rilo), Minneapolis (Shinichi Matsumoto / Bernhard Hering), and Würzburg (Karin Ulrichs) — for further details in preparing this custom-made Iodixanol-UWS solution, and for obtaining ingredients such as Pentastarch.

I shared both our detailed work procedure for preparing this Iodixanol-UWS density gradient and made arrangements with Pentastarch suppliers on various continents to guarantee delivery to other islet centers around the world.

Bernhard J. Hering, from the Minneapolis islet center, was the first, in November 1997, to email me great feedback on this custom-made Iodixanol-UWS solution:

‘Dear Michael: It was a pleasure meeting in Milan a few weeks ago. Hope all is going well in Leiden. We have tested your new gradient for pig islet isolation several times. Without a question this gradient works. As a matter of fact, the first diabetic pig that received allogeneic islets prepared with the new gradient became normoglycemic immediately after transplantation. …’
Bernhard J. Hering, University of Minnesota, Minneapolis, Tue, 11 Nov 1997

We reported our first series of islet xenotransplants of adult pig islets prepared in Iodixanol-UWS in January 1998 at the 17th Workshop of the AIDSPIT Study Group in Igls, Austria (22).

In April–May 1998, finally, a first series of human islet purifications with the novel Iodixanol-UWS density gradient was performed while working with the islet team of Camillo Ricordi during my working visit to the “fast track” center of the Diabetes Research Institute (DRI) at the University of Miami (2,3,4).

In May 1998, Shinichi Matsumoto, working with the Minneapolis team, reported their first successful series of single-donor allo-transplants of pig islets isolated with the Iodixanol-UWS purification method (17,18).

Of note: this Minneapolis team would also be the first to publish an impressive series of successful single-donor human islet transplants in Type 1 diabetic patients (19,20), with islet purification in a continuous iodixanol-UWS density gradient — supplemented with L-histidine for extra buffering — the method of choice (21, 33) for the more recent islet transplantation trials of the NIH (National Institutes of Health) Clinical Islet Transplantation (CIT) Consortium.

Nycomed Collaboration

In late May 1998, after my working visit to Miami, I contacted Nycomed’s density gradient team – product manager Bjørn Henriksen and research consultant and biochemist John Graham – to describe our work and request iodixanol powder. The aim was to test whether the purification solution could be prepared by dissolving the iodixanol powder directly in standard-strength UW solution, avoiding the need for “homemade” double-strength UWS and thereby simplifying clinical application in islet transplantation.

This marked the start of our long-standing collaboration. Bjørn Henriksen immediately sent me the iodixanol powder and put me in contact with biochemist Terry Ford, also a research consultant for Nycomed’s density gradient media, for assistance with the technical details of preparing the iodixanol powder solution in UWS. His fellow advisor John Graham suggested putting together a Nycomed Application Sheet based on our Iodixanol-UWS gradient work using Optiprep (iodixanol).
This application sheet would allow me to publish, in detail, our procedure for islet preparation in UWS, preparation of the Optiprep-UWS density gradient, preconditions, and contact information on Pentastarch suppliers.

We started writing in June 1998, and in September 1998 published the first edition of this Nycomed Application Sheet as: Purification of islets of Langerhans from porcine pancreas. Optiprep™ Application Sheets (No 2.13) Nycomed Pharma AS, Oslo, Norway, Sept. 1998 (23; 1MEMO_20260623_4).

In 2000, when Axis-Shield had taken over responsibility for these density gradient media, a new edition of the Application Sheet was published with minor modifications and a new ‘C15’ catalogue number, as: C15 Purification of Islets of Langerhans from Porcine Pancreas. Optiprep™ Application Sheets (C15) Axis-Shield PoC AS, Oslo, Norway, Nov 2000 (24; 1MEMO_20260623_5).

In 2003, this application was described in our open-access online paper in The Scientific World Journal: Iodixanol Density Gradient Preparation in University of Wisconsin Solution for Porcine Islet Purification (25).

In 2004, a revised edition of the Axis-Shield C15 Application Sheet followed, listing the numerous applications of the methodology in islet centers, adapted and extended for islet isolation from pancreases of other species, and modified for use in the Cobe 2991 centrifuge rather than tubes. Full text PDF (1MEMO_20260623_6) for viewing and downloading below (26).

The 2007 edition — renamed ‘C15 Purification of Islets of Langerhans from porcine, primate and rodent pancreas’ — included the latest references. Full text PDF (1MEMO_20260623_7) for viewing and downloading below (27).

Currently, a less extensive 2020 edition of this Application Sheet is found online, renumbered C16, and renamed ‘Purification of Islets of Langerhans from porcine, primate and rodent pancreas in a discontinuous iodixanol gradient’ (28).

Iodixanol Powder in UW Solution

Making up iodixanol solutions from iodixanol powder is not simple — the process requires heating to around 80 degrees and slow, controlled cooling to prevent crystallization.

In June 1998, both Terry Ford (working in the UK) and I (working in our Leiden Islet Lab) started experiments dissolving 30% (w/v) iodixanol powder in UWS — the same iodixanol concentration used in our standard procedure for preparing the Working Solution by mixing OptiPrep with an equal volume of double-strength UWS (see the Optiprep Application Sheet, Ref. 23; 1MEMO_20260623_4).

I wasn’t able to prepare a 30% iodixanol solution in ViaSpan — the clinically used commercial UWS. Although temperature was carefully controlled, the solution became turbid during the process of dissolving the powder. Terry Ford succeeded in preparing a clear 30% iodixanol solution in a modified UWS (using a different hydroxyethyl starch, not the Pentastarch/Viastarch), but Terry also ran into issues later, in September 1998, when trying to make up a 10% iodixanol solution in Viaspan — the solution was cloudy.

I checked with the NPBI International company in Holland, which produced the ViaSpan solution for DuPont, as to whether such heating might affect the ViaSpan components, and learned that no damage was expected.

In August 1998, I succeeded in preparing a clear 11% solution of the iodixanol powder in ViaSpan (density 1.10) — perhaps a hint of haziness after dissolving the iodixanol, but no issues upon 0.45 µm filtration, so it was considered a clear solution. This solution could be used as the bottom solution of the gradient, by first pelleting the tissue (digest) before resuspension in this 11% ‘working solution’.

Next, in August 1998, in a pilot with two pig pancreases, that 11% iodixanol powder in ViaSpan solution was used as the bottom solution of density gradients (1.100-1.090-1.085-UWS) for islet purification, and showed a similarly successful outcome in a head-to-head comparison with our ‘conventional’ Optiprep-UWS gradients. It appeared that the powder-based gradient worked equally well.

In conclusion: although the powder-based iodixanol gradient worked well in the pilot, making up iodixanol solutions from a powder is not easy, and the way we were making the solutions with Optiprep was the easier of the two alternatives — and, above all, a safe choice for the time being, given the imminent start of our clinical islet transplantation project, with few options for new experiments.

Optiprep (Iodixanol) in ViaSpan

A simpler approach was tested in 1998 that would eventually become the method of choice in 2001, when we started human islet isolation in our GMP cleanroom facility for clinical islet transplantation: mixing the iodixanol solution with the crude islet suspension (digest) in ViaSpan.

Since it might not be necessary to use double-strength UWS, creating the density gradients by mixing only Optiprep and ViaSpan would be the simplest approach, avoiding the need to set up GMP production of the custom-made double-strength UWS for clinical application in islet transplantation.

In fact, mixing Optiprep (60% iodixanol in water) and ViaSpan to create the roughly 1.09 density solution used for human islet purification, has a negligible effect on the ViaSpan composition — only a 10% dilution of the ViaSpan components. Although it does not seem necessary to use double-strength UWS, osmolarity is obviously lower without it, affecting the density of islet and acinar tissue and requiring different gradient densities for purification.

In September 1998, this density gradient of Optiprep (Iodixanol) in ViaSpan was tried in a short pilot of islet purification from adult pig pancreases, in a head-to-head comparison with our standard procedure (including the double-strength UWS). In this simpler new method, OptiPrep (5 ml) was mixed directly with ViaSpan (26 ml) containing the digested pancreatic tissue (‘digest’) to obtain the 1.090 density bottom solution in a 4-step gradient, with densities 1.090-1.085-1.080-ViaSpan (UWS).
Both purification methods yielded similar results in this pilot: a 70–100% recovery of islets, with 70–100% purity.

This simple method was not tested further at the time, because priority was given to advancing GMP production of our standard Iodixanol-UWS medium, which, due to its higher osmolarity, seemed to offer a better guarantee of effective purification in the upcoming human islet isolations, given the greater diversity of human donor pancreata.

IsletPrep

Meetup — Friday, September 25th, 1998: a first meetup with Bjørn Henriksen, Terry Ford, and myself was arranged at the Leiden Islet Laboratory to further discuss the different iodixanol solutions and a possible commercialization of this solution for isolation of Islets of Langerhans. We shared samples of some of the recent UWS2x solutions used in the Leiden Islet Lab, and a hydroxyethyl starch (HES) to potentially replace the proprietary Pentastarch in the commercial solution, along with a first edition of the Application Sheet. Both the content (formulation of the double-strength UWS), packaging, and the potential market for the commercial solution were discussed.

Market — In October 1998, I contacted, via email, 15 of the larger islet centers around the world to explore the potential market. Based on responses from 11 centers (Giessen, Germany; Leicester, UK; Geneva, Switzerland; LA, USA; Miami, USA; Memphis, USA; Perugia, Italy; Edmonton, Canada; St Louis, USA; Brussels, Belgium; Leiden, Netherlands), on average around 1000 large mammal (including human) pancreases were processed per year across these centers. The ‘safe estimate’ of the total number of large mammal pancreases processed per year worldwide amounted to 1500. For the processing of 1000 pancreases in centers showing interest in the gradient, around 150 L of Working Optiprep Solution (WOP) would be required — 75 L double-strength UWS (UWS2x) and 75 L OptiPrep. This did not count the large number of rodent pancreata.

IsletPrep — In October 1998, Bjørn Henriksen coined the term ‘IsletPrep’ for the solution we considered best to supply: the WOP mixture of equal volumes of double-strength UWS (UWS2x) and OptiPrep, in 200 ml bottles.
He planned to have his Pilot Plant produce a small batch of our WOP, and hoped to have IsletPrep available sometime the following year. In the meantime, I could announce that Nycomed planned to introduce an IsletPrep based on our work.

Regarding the formulation of UWS2x, I suggested leaving out the allopurinol, glutathione, and adenosine. Generally, allopurinol and adenosine have not been shown to contribute to organ preservation. Glutathione appears to be beneficial for long-term organ preservation; however: first, the gradient is used only for a short period of time; second, assuming the IsletPrep is mixed with regular UWS, glutathione will be present anyway.

Terry Ford had retired by the end of October but was still available for assistance.

Powerful Tool for Human Islet Purification

From January 1999, I started announcing Nycomed’s plan to produce the working Optiprep-UWS solution in presentations — first at the January 1999 AIDSPIT workshop in Igls, Austria (29) — and in correspondence with other islet centers I was assisting in implementing the procedure. To assist the UK islet centers in Leicester (Heather Clayton) and Oxford (Harold Contractor, Derek Gray), I shipped the WOP solution February 1999.

In February 1999, a few weeks before we received the green light for the official launch of the clinical islet transplantation project at our Leiden University Medical Center (LUMC), a pilot was started testing the innovative Iodixanol-UWS density gradient solution for non-human primate islet isolation, using four macaques, achieving 94% purity and 90% recovery (35).

Clinical Islet Transplantation Project

In February 1999, the Leiden University Medical Centre (LUMC) Executive Board approved our Surgery Department’s clinical islet transplantation project, which we started in March 1999 with the successful isolation and purification of human islets using our Iodixanol-UWS gradient in the Human Islet Laboratory (1MEMO_20260623_1).

The outcome of that first series of human islet isolations at the LUMC was published later that year (30) and presented at the 19th AIDSPIT Workshop, Jan 2000, Igls, Austria (31) — a post on that first series is being prepared.

A second meetup, in March 1999, at the Leiden Islet Laboratory (LUMC) was arranged with Bjørn Henriksen, Terry Ford, and myself to further discuss the exact formulation of ‘IsletPrep’.

In 2000, when Axis-Shield had taken over responsibility for these density gradient media, Bjørn Henriksen supplied the HES for the final IsletPrep formulation that I worked out and used successfully for islet purification in a second series of human islet isolations, which we started in 2000 using the automated Ricordi method in our laboratory. (A post on that second series is being prepared.)

Eventually, in 2001, when we started in the GMP cleanroom facility of our Human Islet Isolation Laboratory at the Leiden University Medical Center (LUMC), the method of choice for islet purification became our simple procedure of mixing the clinically cGMP-approved solutions of iodixanol (Visipaque) and UWS (ViaSpan).

Optiprep wasn’t yet a GMP-certified product at the time, and therefore had to be replaced by the similar Visipaque (65% iodixanol) solution, which is cGMP-certified and used in patients as a contrast agent — even though both Optiprep and Visipaque were produced from the same batches of iodixanol (personal communication with Bjørn Henriksen).

Note that this purification method was recently adapted for the automated ‘PRISM’ method at the LUMC, replacing the dimeric Iodixanol (Visipaque, Optiprep) in UWS , with the chemically similar monomeric Iopromide (Ultravist) in UWS (34).

References

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5) Rickwood D, Ford T, Graham J. Nycodenz: a new nonionic iodinated gradient medium. Anal Biochem. 1982 Jun;123(1):23-31. doi: 10.1016/0003-2697(82)90618-2. PMID: 7114474.

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10) Van der Burg MPM, Guicherit OR, Prins FA, Scherft JP, Frölich M, Gooszen HG. Percoll in UW: efficient iso-osmotic canine and human islet purification. 5th Congres European Society for Organ Transplantation, Maastricht (The Netherlands) October 7–10, 1991. Online in: Percoll UWS Purification Pancreatic Islets • ESOT 1991 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20250114 • URL michelvanderburg.com/2025/01/14/

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13) Van der Burg MPM, Guicherit OR, Frölich M, Prins FA, Bruijn JA, Gooszen HG. Cell preservation in University of Wisconsin solution during isolation of canine islets of Langerhans. Cell Transplant. 1994 Jul-Aug;3(4):315-24. doi: 10.1177/096368979400300408. PMID: 7921636. In: Chapter 4 of Pancreatic islet transplantation. Michel van der Burg. Thesis Leiden University (1994; see Reference 11) | URL Chapter 4 direct link https://scholarlypublications.universiteitleiden.nl/access/item%3A3486611/download

14) Van der Burg MPM, Basir I, Bouwman E. Non-traumatic porcine islet density gradient purification in a novel iodixanol in University of Wisconsin solution. The 4th Int. Congress for Xenotransplantation, Nantes (France) Sept. 7–11, 1997. Online in: Purification Islets in Iodixanol-UWS • Leiden Start 1996 • Michel van der Burg • Miracles.Media • @1MEMO 20250126 • URL michelvanderburg.com/2025/01/26/

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16) Van der Burg MPM, Basir I, Bouwman E. No porcine islet loss during density gradient purification in a novel iodixanol in University of Wisconsin solution. Sixth Congress of the Int. Pancreas and Islet Transplant Association (IPITA), Milan (Italy) Sept. 24–27, 1997. Online in: Innovative Islet Purification in Iodixanol-UWS • IPITA 97 • Michel van der Burg • Miracles.Media • @1MEMO 20250128 • URL michelvanderburg.com/2025/01/28/

17) Matsumoto S, Zhang H J, Gilmore T, van der Burg MPM, Sutherland DER, Hering BJ. Large scale isopycnic islet purification utilizing non-toxic, endotoxin-free media facilitate immediate single-donor pig islet allograft function. Presentation at the 24th Annual Scientific Meeting of the American Society of Transplant Surgeons, Chicago (USA) May 1998. 24th ASTS Program book, Abstract #A-120 • 1MEMO_20260326_5 • Michel van der Burg • Miracles.Media • In: 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/

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21) NIH CIT Consortium Chemistry Manufacturing Controls Monitoring Committee; NIH CIT Consortium. Raw Material Specification, Cold Storage/Purification Stock Solution. CellR4 Repair Replace Regen Reprogram. 2016;4(3):e1914. Epub 2016 May 29. PMID: 30613730; PMCID: PMC6319875. URL (full text) https://pmc.ncbi.nlm.nih.gov/articles/PMC6319875/pdf/nihms-996504.pdf

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23) 1998 Optiprep Application Sheet 2.13 • 1MEMO_20260623_1 • Miracles•Media • TakeNode xxx • 2.13 Purification of Islets of Langerhans from Porcine Pancreas. Optiprep™ Application Sheets (2.13) Nycomed Pharma AS, Oslo, Norway, Sept 1998

24) 2000 Optiprep Application Sheet C15 • 1MEMO_20260623_2 • Miracles•Media • TakeNode xxx • C15 Purification of Islets of Langerhans from Porcine Pancreas. Optiprep™ Application Sheets (C15) Axis-Shield PoC AS, Oslo, Norway, Nov 2000

25) Iodixanol Density Gradient Preparation in University of Wisconsin Solution for Porcine Islet Purification. ScientificWorldJournal. 2003 Dec 1;3:1154-9. doi: 10.1100/tsw.2003.107. PMID: 14646009; PMCID: PMC5974767. URL (full text) https://onlinelibrary.wiley.com/doi/10.1100/tsw.2003.107

26) 2004 Optiprep Application Sheet C15 • 1MEMO_20260623_6 • Miracles•Media • C15 Purification of Islets of Langerhans from porcine pancreas. Optiprep™ Application Sheets (C15) Axis-Shield PoC AS, Oslo, Norway, Oct 2004. Full text PDF for viewing and download below 1MEMO_20260623_6.

27) 2007 Optiprep Application Sheet C15 • 1MEMO_20260623_7 • Miracles•Media • C15 Purification of Islets of Langerhans from porcine pancreas. Optiprep™ Application Sheets (C15) Axis-Shield PoC AS, Oslo, Norway, Nov 2007. Full text PDF for viewing and download below 1MEMO_20260623_7.

28) 2020 Optiprep Application Sheet C16 • 1MEMO_20260623_4 • Miracles•Media • Purification of Islets of Langerhans from porcine, primate and rodent pancreas in a discontinuous iodixanol gradient. Optiprep™ Application Sheet C16; 9th edition, January 2020. Serumwerk Bernburg AG, Bernburg, Germany, Oct 2004. URL (full text PDF) https://diagnostic.serumwerk.com/wp-content/uploads/2021/05/C16-Serumwerk.pdf

29) Van der Burg MPM, Ranuncoli A, Molano R, Kirlew T, Ringers J, Bouwman E, Ricordi C. Efficacy of the novel iodixanol-UWS density gradient for human islet purification. 18th Workshop AIDSPIT, Igls (Austria) Jan. 24-26, 1999 . In : 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/

30) 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 1999 Dec; 36: 230. URL https://doi.org/10.1007/s005920050168

31) 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. Talk at the 19th Workshop of the Study Group on Artificial Insulin Delivery Systems, Pancreas and Islet Transplantation (AIDSPIT) of the European Association for the Study of Diabetes (EASD). Acta Diabetol 36, 205–231 (1999). https://doi.org/10.1007/s005920050168

32) Soper CPR, Ford TW, Bending MR. Satisfactory islet isolate number and viability with Iodixanol [Optiprep] discontinuous gradient centrifugation. Horm Metab Res Suppl 1995; 27: 61. Abstract poster presentation at the 14th Workshop of the Study Group Artificial Insulin Delivery Systems, Pancreas and Islet Transplantation (AIDSPIT) of the European Association for the Study of Diabetes (EASD). Igls, Austria, 30-31 January 1995. Abstracts. Horm Metab Res. 1995 Jan;27(1):47-66. PMID: 7729796.

33) Ricordi C, Goldstein JS, Balamurugan AN, Szot GL, Kin T, Liu C, Czarniecki CW, Barbaro B, Bridges ND, Cano J, Clarke WR, Eggerman TL, Hunsicker LG, Kaufman DB, Khan A, Lafontant DE, Linetsky E, Luo X, Markmann JF, Naji A, Korsgren O, Oberholzer J, Turgeon NA, Brandhorst D, Chen X, Friberg AS, Lei J, Wang LJ, Wilhelm JJ, Willits J, Zhang X, Hering BJ, Posselt AM, Stock PG, Shapiro AM, Chen X. National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities. Diabetes. 2016 Nov;65(11):3418-3428. doi: 10.2337/db16-0234. Epub 2016 Jul 27. Erratum in: Diabetes. 2017 Sep;66(9):2531. doi: 10.2337/db17-er09a. PMID: 27465220; PMCID: PMC5079635.

34) 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://journals.lww.com/transplantjournal/fulltext/2022/06000/prism__a_novel_human_islet_isolation_technique.28.aspx

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

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