Pancreatic Islet Isolation With UW Solution • A New Concept • 20241224

Michel van der Burg • 20241224 • Last update 20241228-1614

In November 1989 in Barcelona, I had my first opportunity to present a paper at a major international organ transplantation meeting — the 4th ESOT — focusing on the rationale for using the UW organ preservation solution during pancreatic islet isolation.

Poster lost

Excited about giving a talk and poster presentation at this 4th ESOT congress in Barcelona, ​​I forgot to take my poster from the overhead compartment of the plane upon arrival in Barcelona. A new poster was made on the spot at the Sandoz booth in the congress venue, by cut and paste work using the manuscript of the congress proceedings paper (PMID 2202137) and enlargement with a Sandoz A3 photocopier.
Due to design constraints, the author affiliation info was omitted, and the Du Pont logo was added (image 20241025_1).

Barcelona ’89 poster remastered

That photo of the poster board in Barcelona (20241025_1) was used for creating this digitally remastered poster presented here (20241025_2) — which now includes the complete manuscript, as well as the Du Pont logo ;)

The Nov ’89 Barcelona publications, were the first ones dedicated to presenting the concept , the rationale, for using the UW organ preservation solution during pancreatic islet isolation.

This wasn’t the first time we reported the news of our results with this new, innovative, method developed in our pre-clinical model for the isolation and purification of pancreatic islets of Langerhans for transplantation in diabetic patients. Below that background, publications, and papers available for download.

Background

I was well aware of the development in the late 80s by Belzer’s team at the University of Wisconsin in Madison (USA) of the new solution to preserve pancreas donor organs during cold storage for transplantation :

In 1986 the Belzer team had reported on the newly developed cold storage solution for pancreas preservation, the University of Wisconsin (UW) Solution (1).

From 1986 our colleague Rutger Ploeg (from the Department of Surgery of Leiden University) had been doing PhD research in Belzer’s organ preservation laboratory in Madison. He introduced the ‘…new cold storage solution, the “UW-Solution” in a letter Dec. 10th, 1987 to all Eurotransplant centres (2), and I had assisted during Rutger Ploeg’s preservation research in Madison on the UW solution in pancreas transplantation in dogs, by calculating the k-values ​​of glucose tolerance (3,4).

1) Wahlberg JA, Southard JH, Belzer FO. Development of a cold storage solution for pancreas preservation. Cryobiology. 1986;23(6):477–482.

2) Alexandre G, Margreiter R, Persijn GG, Pichlmayr R, Terpstra JL, Ploeg RJ. To all Eurotransplant centres : Introduction new cold storage solution, the “UW-Solution”. Letter Dec 10, 1987 , Ploeg RJ, Department of Surgery, University Hospital Leiden (AZL , now LUMC).

3) Ploeg RJ, Goossens D, Sollinger HW, Southard JH, Belzer FO. Efficacy of 48-hour pancreas preservation with UW solution in the dog allograft model. Transplant Proc. 1988 Oct;20(5):1026-8. PMID: 3055478.

4) Ploeg RJ. Preservation of kidney and pancreas with the UW solution : experimental and clinical studies. (Thesis, Leiden University), ‘s-Gravenhage : Pasmans (ISBN 9090042490), 1991: 231 p. URL https://search.worldcat.org/en/title/65672513

First thought

In early 1989, I wondered how our research, into improving the technique of pancreatic islet isolation, could benefit from the great interest in this new organ preservation solution, and the contacts through Ploeg with both the Belzer laboratory and Du Pont (Du Pont Critical Care, Waukegan, USA), the manufacturer of the commercial UW Solution.

Radical choice

The most logical , traditional, choice would be, to investigate organ preservation of the pancreas prior to pancreatic islet isolation. However, logistically, this seemed to be too much of a change in our research.
Therefore, in February 1989, I made the radical choice of testing the UW Solution as a replacement for conventional isolation solutions in our preclinical transplantation model of canine islet isolation.

Start

A research plan was drawn up for Du Pont (Robert Carter, Clinical Research Project Coordinator, DuPont, UK), and we started our work March 1989. At first — the first two islet isolation experiments — the UW Solution was only used at the first stage of the isolation procedure, as the collagenase solution for pancreatic injection, transport, and digestion in the laboratory.
From April 1989 on, the UW-Solution was used in all our isolation steps, both before density gradient purification, and also for washing the purified islets.

Rationale

The research started in April 1989 with the rationale , that : because the UW-Solution (UWS) protects the viability of the pancreas during cold storage, the UWS can also improve the yield of viable isolated islets, because islet isolation also takes place mainly at low temperature.

Discovery

However, from the first time in April 1989 that the UW-Solution was used during all isolation steps, the tissue immediately appeared different, with almost complete islet purification due to a clear difference in islet density and the darker and more compact looking exocrine pancreatic tissue, compared to the previous conventional isolations.

I did not expect this… but I understood it immediately, even during that first isolation: the effect of UWS during the isolation, the effect on the density, by counteracting cell swelling of especially the other, exocrine, pancreatic tissue, resulting in that tremendous improvement in the purification of islets.

News

The news of the exciting finding of over 90% purity of these UWS-isolated islets was brought first that month, April 1989, during my oral presentation (5) at the General Surgery Science Days, the yearly meeting on the current scientific research taking place at the Department of Surgery of the Leiden University Hospital (now LUMC) in Leiden , Holland .

5) Van der Burg MPM. New methods of islet isolation – a comparative study (dutch : ‘Nieuwe methoden van eilandisolatie – een vergelijkend onderzoek). General Surgery Science Days 1989, Leiden University Hospital (dutch : Wetenschapsdagen Algemene Heelkunde 1989, AZL), Leiden, (The Netherlands) April 28, 1989. Yearly meeting on current research at the Department of Surgery of the Leiden University Hospital (now LUMC) in Leiden , Holland .

Next, a manuscript was submitted June or July 1989 for publication of a Letter in The Lancet (6)… but was rejected.

6) Van der Burg MPM, Gooszen HG, Ploeg RJ, Guicherit OR, Scherft JP, Terpstra JL, Bruijn JA, Frölich M. Pancreatic islet isolation with UW solution: a new concept. Manuscript submitted June/July 1989 for publication as Letter in The Lancet. (rejected).
Report online in : Lancet Letter 1989 UW Solution Islet Isolation | 20220823 | Michel van der Burg | michelvanderburg•com

Islet transplantation

Internationally , the news of both our first pre-clinical islet transpant, and the islet purification success when using UWS during islet isolation, was first reported July 8, 1989 at the Anglo Danish Dutch Diabetes Group meeting in Oxford, UK (7). National news reports appeared first September ’89 in the Cicero magazine (8) , and Oct ’89 in the Dutch newspaper Leidsch Dagblad (9).

7). Van der Burg MPM, Gooszen HG, Scherft JP, Terpstra JL, Frölich M, Guicherit OR, Lemkes HHPJ, Bruijn JA. The isolation of canine pancreatic islets for transplantation. Seventh Annual Meeting Anglo Danish Dutch Diabetes Group, Oxford (UK) July 5–9, 1989.
Report online in : ADD Diabetes Group 1989, St Edmund Hall, Oxford • Michel van der Burg • Miracles•Media • 20241019 • michelvanderburg•com

8), ‘Eilandjes’ getransplanteerd | by Sylvia van Leeuwen in Cicero, Sep. 15th, 1989 (ISSN 0920-2900), the biweekly publication of the Academic Hospital and Leiden Medical Faculty | 20240830_3 • michelvanderburg•com
Report online : Islet Transplantation Breakthrough in Leiden University Hospital • 20240830 • Michel van der Burg • michelvanderburg•com

9). Doorbraak in onderzoek naar behandeling suikerpatiënten. Ontdekking door artsen Leids Academisch Ziekenhuis. (EN tr. “Breakthrough in research into treatment of diabetics. Discovery by doctors of Leiden University Hospital”) | by Gert Visser, in Leidsch Dagblad, Oct 24, 1989 | Dutch newspaper.
Report online : Islet Transplantation Breakthrough in Leiden University Hospital • 20240830 • Michel van der Burg • michelvanderburg•com

Internationally at a major meeting, the UWS news was first presented in a poster presentation September 1989 in Minneapolis (10). The UWS data had been added ad hoc in the poster – that is , it wasn’t part of the accepted abstract. The first proceedings paper on our UWS work was also submitted at that meeting , and was published April ’90 (11).

10). Van der Burg MPM, Gooszen HG, Ploeg RJ, Scherft JP, Field MJ, Guicherit OR, Terpstra JL, Van de Woude FT, Frölich M, Bruijn JA. Comparison of islet isolation techniques in dogs: Over 90% purified islets using UW solution. 4th International Symposium on Organ Procurement and Preservation and 2nd International Congress on Pancreatic and Islet Transplantation, Minneapolis (USA) September 17–22, 1989
Report online in : Minneapolis 1989 Poster | 20240804 | Michel van der Burg | michelvanderburg•com

11). Van der Burg MPM, Gooszen HG, Ploeg RJ, Scherft JP, Field MJ, Guicherit OR, Terpstra JL, Van de Woude FJ, Frölich M, Bruijn JA. Comparison of islet isolation techniques in dogs: Over 90% purified islets using UW solution. Transplant Proc. 1990 Apr;22(2):795-6. PMID: 2158174.
This paper appears to be not readily available online – a reprint copy is available here PMID_2158174 🔗

A new concept – Nov 1989 , Barcelona, Spain – 4th ESOT

Finally , November 1989 in Barcelona, Spain – at the 4th ESOT meeting – the first presentations followed, focussing on the concept — the rationale — for using the UW organ preservation solution during pancreatic islet isolation — in the book of abstracts (12), the poster shown above (13) that was created from the proceedings paper submitted at this meeting (14), and , I included this UWS work also ad hoc in the talk delivered at this meeting on comparison of islet isolation techniques (12, 15, 16). I plan to post on that talk soon.

As reported in our poster and the manuscript delivered in Barcelona of our paper ‘Pancreatic Islet Isolation With UW Solution: A New Concept’ we had been using collagenase in UW solution in this first short (n=4) series of experiments.

Please note, that I changed the description of the collagenase solution to Hanks’ solution (HBBS) when editing the author proof edition shortly before publication of the final paper August 1990 (PMID_2202137 ; 14) — to best convey our current insights and practice.

For hypothetical reasons only — because the UWS was expected to be detrimental perhaps to cell viablity at the higher temperatures during collagenase digestion of the pancreas (the first stage of islet isolation) — I decided to change the collagenase solution in June 1989 when I began a new series of islet isolations for our first canine islet transplants. From that point on, a modified Hanks’ solution was used for collagenase (17).

We did not observe a difference at the time* , whether using one or the other solution for collagenase digestion , with respect to either islet purity, recovery, or viability at islet isolation and days later in culture.

Years later , collagenase in UWS was chosen for the isolation of pig islets, in experiments with a long cold ischemia time of the pancreas during transport with distant pancreas procurement from sows in a slaugtherhouse — Ballering (distant family) in Son — near the south border of The Netherlands, with injection of cold collagenase solution before transport, with the aim of better preservation of the islets (18).

12) Excerpt from book of abstracts 4th Congress of the European Society for Organ Transplantation, Barcelona (Spain) November 1–4, 1989 , including the abstracts :
– Van der Burg MPM, Gooszen HG, Guicherit OR, Ploeg RJ, Scherft JP, Terpstra JL, Bruijn JA,
Frölich M. UW solution as the isolation medium markedly improves canine islet isolation (abstract).
– Van der Burg MPM, Gooszen HG, Field MJ, Scherft JP, Terpstra JL, Van de Woude FT, Guicherit OR, Frölich M, Bruijn JA. Comparison of current islet isolation techniques in dogs (abstract). Excerpt ESOT abstracts book available here 19891101_ESOT 🔗

13) Van der Burg MPM, Gooszen HG, Ploeg RJ, Guicherit OR, Scherft JP, Terpstra JL, Bruijn JA, Frölich M. Pancreatic islet isolation with UW solution: a new concept. 4th Congress of the European Society for Organ Transplantation, Barcelona (Spain) November 1–4, 1989. Poster presentation.
Report online (here) : Pancreatic Islet Isolation With UW Solution – A New Concept • 20241224 • Michel van der Burg • michelvanderburg•com
PDF poster — M.P.M. van der Burg • Miracles.Media • 20241025_2 • TakeNode 661fade9-51a7-42b1-a7e1-1e281f74ad6d — available here 20241025_2 🔗

14) Van der Burg MPM, Gooszen HG, Ploeg RJ, Guicherit OR, Scherft JP, Terpstra JL, Bruijn JA, Frölich M. Pancreatic islet isolation with UW solution: a new concept. Transplant Proc. 1990 Aug;22(4):2050-1. PMID: 2202137.
This paper appears to be not readily available online – a reprint copy is available here PMID_2202137 🔗

15) Van der Burg MPM, Gooszen HG, Field MJ, Scherft JP, Terpstra JL, Van de Woude FT, Guicherit OR, Frölich M, Bruijn JA. Comparison of current islet isolation techniques in dogs. 4th Congress of the European Society for Organ Transplantation, Barcelona (Spain) November 1–4, 1989. Oral presentation.

16) Van der Burg MPM, Gooszen HG, Field MJ, Scherft JP, Terpstra JL, van de Woude FJ, Guicherit OR, Frölich M, Bruijn JA. Comparison of current islet isolation techniques in dogs. Transplant Proc. 1990 Aug;22(4):2044-5. PMID: 1697121.
This paper appears to be not readily available online – a reprint copy is available here PMID_1697121 🔗

17) Michael P.M. van der Burg. Pancreatic islet transplantation: studies on the technique and efficacy of islet isolation and transplantation. (Doctoral Thesis, Faculty of Medicine, Leiden University Medical Center (LUMC) , Leiden University), Boskoop: M.P.M. van der Burg | Miracles.Media (ISBN electronic, pdf, 9789080216402 ; ISBN print 9789080216419, 9080216410), 1994: 192 p. Leiden University https://catalogue.leidenuniv.nl/permalink/31UKB_LEU/18s393l/alma9940161419602711

18) Van der Burg MPM, Graham JM. 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.

*Audio of data discussion posted in : Percoll UWS Purification Pancreatic Islets • ESOT 1991 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20250114 • URL michelvanderburg.com/2025/01/14/

Updates

20241227-1329 Better copy of Minneapolis proceedings paper replaces PMID_2158174

20241228-1614 Author Proof section on the collagenase solution changes

*20250124-0244 Added reference to audio of data discussion posted in : Percoll UWS Purification Pancreatic Islets • ESOT 1991 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20250114 • URL michelvanderburg.com/2025/01/14/

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