4th ESOT Slide #19 • Pancreatic Islets UWS Series 1989 • Kodak PhotoCD • Michel van der Burg • Miracles.Media • 20250103_1 • TakeNode eeb55729-c02b-4f73-ab0e-9f71b65bf85e
Slide #19 of talk by Michel van der Burg at the 4th ESOT congress in Barcelona (Spain) Nov 1989 on the paper ‘Pancreatic Islet Isolation With UW Solution • A New Concept’ (1,2). Details of this talk were posted recently (2) with a scan of a paper print of slide #19 – slighly cropped with printing. Here the full image of the original slide, scanned by Kodak PhotoCD in 1994, with minor color correction added (20250103_1) in this post.
This ‘Slide #19’ shows the final dithizone stained sample of the UW-isolated islets after dextran density gradient purification — a micrograph made April 18, 1989 , the second islet isolation experiment performed using the UW-Solution as the isolation solution.
In the lab journal of the first isolation experiment with UW-Solution, Wednesday April 12th 1989, I noted on the final purified islet preparation : ‘handpicking for encapsulation was not necessary: preparation more than 90% pure ( translated from dutch : “handpicken voor inkapseling was niet nodig: preparaat meer dan 90% zuiver”)’.
‘Handpicking’ of islets had been done at the start of our islet lab in 1985-1987 for counting rodent islets in cell culture dishes, and monitoring islet insulin secretion in tubes (3). Soon, ‘handpicking’ was no longer needed , when monitoring the insulin secretion of isolated islets in perifusion chambers (4,5). However, the handpicking method was used again in a pilot study on encapsulation of islets in 1989 by medical student Joost Clemens (6). Joost had just started on this research project, and was assisting me with islet ‘counting’ (yield and purity assessment) in the ‘duplo’ samples from this first series of UWS isolations.
Handpicking Pancreatic Islets • Michel van der Burg • Miracles.Media • 20250103_2 • TakeNode 7988ce39-6777-4db3-82c5-8191acdb13d6
Macro photography (Photo paper print, September 1987, AVC, Leiden University) of the aspiration of isolated canine pancreatic islets, in a suspension still contaminated with exocrine pancreatic fragments, at the tip of a hand blown glass handpicking pipette (custom made at the Leiden University) collected and transferred into tubes for monitoring insulin secretion the first year of pilot work in the Leiden islet laboratory (4).
2) Pancreatic Islet Isolation in UW Solution & Transplantation • ESOT 1989 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20241229 • URL michelvanderburg.com/2024/12/29/
3) Lucky #1 Islet • 20240811 • Michel van der Burg • michelvanderburg•com
4) Cradle of Islet Transplants • 20240829 • Michel van der Burg • michelvanderburg•com
5) Monitoring pancreatic islets in perifusion • 20240911 | Michel van der Burg | michelvanderburg•com
6) Joost A.M. Clemens (MSc student in Medicine) at the Department of Biomaterials (Prof. dr K. de Groot) and Department of Surgery of the Leiden University (Michel van der Burg , Hein Gooszen). Pilot study of the encapsulation of dog islets using the alginate polylysine and poly-HEMA-phospate method (1989). At that time , both the Biomaterials department and the Islet Lab of the Surgery department were housed in the building of the Cell Biology department of the Leiden University Hospital (AZL, now LUMC). Below a portrait snapshot I took of Klaas de Groot at a Garden party organized in 1989 by the Department of Cell Biology, Leiden University.
Klaas de Groot, Biomaterials Department of the Leiden University in 1989. Photo by Michel van der Burg • Miracles.Media • 20250103_3 • TakeNode c25a87b7-09a4-49ce-8c42-14142da1e066
Citation info : Pancreatic Islets UWS Series 1989 • Kodak PhotoCD • Michel van der Burg • Miracles.Media • @1MEMO 20250103 • URL michelvanderburg.com/2025/01/03/
Oral Presentation Slide 19 ~ Pure Islets Isolated in UW Solution • Miracles.Media • 20241229_1 • TakeNode ce420e5a-1df7-4e4f-bcb6-6831434ffac7
In November 1989, I had my first chance for a presentation at a major international conference, the 4th ESOT meeting in Barcelona, of a paper centered on the rationale for employing the University of Wisconsin (UW) organ preservation solution in pancreatic islet isolation.
Venue 4th Congress of the European Society for Organ Transplantation, Barcelona (Spain) November 1–4, 1989 • Michel van der Burg • Miracles.Media • 20241224 • TakeNode 103c4c3c-5d36-4111-a5f8-f60e81c5db4d
This innovative islet isolation work with the UW-Solution had been accepted as a poster presentation for the 4th ESOT meeting (1). I also took the opportunity to present this new work during a talk on previous isolation work (2,3) at this conference.
Barcelona Nov 1989 4th ESOT • Talk by Michel van der Burg • Miracles.Media • 20241229_2 • Photo : Grup Jaume Muntaner (Barcelona) • TakeNode 96957e2f-1462-48e1-aca1-4745198d9a54
‘Behind the scenes’ I had first remade my lost poster at the congress venue (1), and then I rewrote my speech in the hotel room on the older research (2) updated with the more recent work with the UW-Solution, and including the outcome of our first islet transplantations.
Barcelona 89 • Handout 4th ESOT Talk
Below a scan of that handout of the final speech, written out at full lenght in a notepad from a recent working visit in Minneapolis (4).
Barcelona 89 • Handout 4th ESOT Talk • Michel van der Burg • Miracles.Media • 20241229_3 • TakeNode f8595a82-fba5-4a89-a01f-4c37976d06d7 • PDF FILE 20241229_3 copy is available here
( finishing speech first part on our previous islet isolation methods using the conventional RPMI solution – a solution originally designed for tissue culture, not for cold storage of organs )
Slide 18
Image Slide 18 (scan of print) • Best (Not Usual) Purity Islets RPMI Series • Miracles.Media • 20241229_4 • TakeNode a6afbf29-b3e6-41d0-abd0-07471303be15
This slide shows one of the purest preparations obtained, with an estimated purity of 65% islets. • On the average however a purity of only 30% was obtained.
Recently we adopted an entirely new approach to islet isolation. • Since UW, the new organ cold storage solution has been shown to allow long-term cold storage of the canine pancreas; • and, since islet isolation too is largely performed in the cold; • we tested this preservation solution as the isolation medium, throughout the isolation procedure in another 6 dogs; • as compared to the commonly used solutions like RPMI tissue culture medium.
Slide 19
Image Slide 19 (scan of print) – Usual Purity Islets UWS Series • Miracles.Media • 20241229_5 • TakeNode dacd3b99-5958-44fe-85ed-6abd55db2676
This slide shows the final dithizone stained preparation after dextran purification of UW-isolated islets. • UW did not affect islet yield • however, UW markedly improved purity : • acinar tissue is virtually absent.
2) 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. (1)
3) 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 at this site (1)
4) Working visit Sep – Oct 1989, joining the pancreatic islet isolation team of the pioneer transplant surgeon David Sutherland at the University of Minnesota in Minneapolis.
Citation info : Pancreatic Islet Isolation in UW Solution & Transplantation • ESOT 1989 Talk • Michel van der Burg • Miracles.Media • @1MEMO 20241229 • URL michelvanderburg.com/2024/12/29/
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).
Scan of the slide picture taken at the 4th Congress of the European Society for Organ Transplantation, Barcelona (Spain) November 1–4, 1989 • Michel van der Burg • Miracles.Media • 20241025_1 • TakeNode 054301b6-0b6e-458c-84f6-0b76e25092d5
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 😉
Poster 4th Congress of the European Society for Organ Transplantation, Barcelona (Spain) November 1–4, 1989 • Digitally remastered from original manuscript of article PMID 2202137 by author, publisher, M.P.M. van der Burg • Miracles.Media • 20241025_2 • TakeNode 124e20db-758a-4bdb-b854-c6cefdb7cc3c
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.
Venue 4th Congress of the European Society for Organ Transplantation, Barcelona (Spain) November 1–4, 1989 • Michel van der Burg • Miracles.Media • 20241224 • TakeNode 103c4c3c-5d36-4111-a5f8-f60e81c5db4d
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/
St Edmund Hall, University of Oxford, July 1989 • Michel van der Burg • Miracles•Media • 20241019_1 • TakeNode af426345-4fb3-48a3-8d5e-4368c56826aa
Venue of the Seventh Annual Meeting of the Anglo–Danish–Dutch Diabetes Group*, Oxford (UK) July 5–9, 1989.
The first international meeting were our new concept was presented, of pancreatic islet isolation in the University of Wisconsin Solution (UW-Solution or UWS) a solution designed recently for preservation of a donor pancreas during cold storage prior to transplantation.
Quote :
“…A few months ago, we adopted an entirely new approach to islet isolation. Recently a new cold storage organ preservation solution was developed at the University of Wisconsin, the UW solution, allowing long term, 24 to 72 h, cold storage of the canine pancreas. Since islet isolation is largely performed in the cold, we tested this preservation solution as the isolation medium throughout the isolation procedure. This slide shows that using the UW solution, purity has increased to over 90%…”
In addition our first successful pre-clinical transplant, we had performed the last month, was reported as breaking news at the end of the talk.
Quote :
“Three weeks ago we did our first autotransplantation of isolated islets from the whole gland by retrograde infusion into the spleen. The dog is doing fine: fasting glucose amounts to 5-6 mM and postprandial glucose between 6-8 mM ; postprandial insulin increases 6-7 fold. Thank you.”
St Edmund Hall, Oxford, 1989, 7th Meeting ADDD Group • Michel van der Burg • Miracles•Media • 20241019_2 • TakeNode ca40adf0-3b86-4ada-93a8-126c6768d420
Notes
Seventh Annual Meeting Anglo Danish Dutch Diabetes Group • Michel van der Burg • Miracles•Media • 20241019_3 • TakeNode bffdea47-9464-4f7b-8299-ec299d41ca4d
* Group supported through the Nordisk UK Professional Programme.
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.
Van der Burg MPM, Gooszen HG, Guicherit OR, Jansen JBMJ, Frölich M, Lamers CBHW. The mechanism of pancreatic duct obliteration induced hyperglycemia. Seventh Annual Meeting Anglo Danish Dutch Diabetes Group, Oxford (UK) July 5–9, 1989.
Citation info : ADD Diabetes Group 1989, St Edmund Hall, Oxford • Michel van der Burg • Miracles•Media • 20241019 • URL michelvanderburg•com
Pancreatic Islet Transplantation • Isolation & Transplantation of Islets of Langerhans • 1988 to early 1990s • Islet Transplant Laboratory • Leiden University Hospital • 20240912_1 (Note 1)
Grants
In 1988, we started a project with unique integration of two important trends in research into the treatment of diabetes by transplantation at the Leiden University Hospital (AZL) in Leiden, with major grants from the dutch Ministry of Welfare, Health and Culture (WVC) and the dutch Diabetes Fund (Diabetes Fonds Nederland).
Grants diabetes research • Newspaper Leidsch Dagblad, June 24, 1988 (Note 2)
The generous grants were received — as reported June 24, 1988 in both the dutch newspaper Leidsch Dagblad (2) and in Cicero, the biweekly publication of the Leiden Medical Faculty and University Hospital (3), as a result of our preliminary research over the previous five years into improving the technique of pancreas transplantation, and more recently the development of a technique for isolating the Islets of Langerhans from the pancreas, which produce hormones such as insulin. The idea behind this is, that these isolated islets, after injection into the body, will restart and maintain insulin production.
Questions
What is the consequence of the loss of normal nerve connections to the islets during transplantation? What are the consequences of transplantation of only a segment of the pancreas, or islet transplantation, when fewer islets are available? What is the consequence after transplantation of the different insulin drainage route, where the insulin does not follow the normal path directly to the liver? To what extent do transplantation procedures disrupt the normal architecture and interactions of islets, the pancreas, and other parts of the gastro-intestinal system, and the blood sugar regulation in the body?
Project
With the hope of answering these questions, the grants supported an ambitious new project supervised by Hein Gooszen, integrating two concomitant PhD projects for detailed islet function studies in both experimental pancreas transplantation, by Onno Guicherit (4) , as well as islet isolation by Michel van der Burg (5) in the same model.
A special feature of the experimental design in this preclinical model is that the results of functional studies in the experimental animal can be compared with such functional studies with the isolated islets from the pancreas, where the direct effect on the islets is investigated during perifusion tests in our laboratory (6).
That same month, June 1988, we began research to improve the method of islet isolation in our laboratory, with the assistance of Jane Field, who had come over that month at our invitation from Minneapolis, where she was a key member of the Surgical Research lab, University of Minnesota (led by David Sutherland).
The introduction of this Minneapolis method for islet isolation significantly improved the yield of isolated islets in our Islet Transplant Lab.
New concept : University of Wisconsin solution (UWS) for islet isolation
Next , early 1989 , our Islet Transplant Lab took a major step forward in a new approach to isolation and purification of the islets by replacing the islet isolation solution (the general used basic physiological salt solution or tissue culture solution) with a novel organ preservation solution : the University of Wisconsin solution (UWS). The method of choice nowadays in clinical islet transplantation centers. More on this introduction of UWS will soon be posted here. A reprint of a first poster presented in Minneapolis, Sep. 1989, is now online here (7).
Program
June 1989 our Surgery Department (Leiden University) started an additional project, for ‘auto’ transplantation of isolated islets : Isolation of the islets from the canine pancreas and transplantation of the isolated islets ca 4 hours later in the same animal (8).
Thus, from 1989, we studied the insulin secretion of the isolated islets in perifusion experiments in the laboratory (‘in vitro’) in comparison with both the islet function ‘in vivo’ after transplantation of the isolated islets, and in the concomitant pancreas transplantation experiments — in support of our clinical pancreas transplantation program in Leiden.
Notes
1) Pancreatic Islet Transplantation • Isolation & Transplantation of Islets of Langerhans • 1988 to early 1990s • Islet Transplant Laboratory • Leiden University Hospital • 20240912_1 • michelvanderburg•com | TakeNode 5b5ca362-2adf-497a-b2be-a83e47617017 | Image edit based on : Pancreatic islet transplantation • Michel van der Burg • Miracles.Media • Thesis Repository Leiden University https://hdl.handle.net/1887/3486604
Captions in Note 9
2) Subsidie voor onderzoek suikerziekte. Leidsch Dagblad, June 24, 1988 (leiden.courant.nu) • 20240912_2 • michelvanderburg•com
3) Diabetesonderzoek | AZL krijgt grote subsidies voor diabetesonderzoek | by Sylvia van Leeuwen in Cicero, June 24th, 1988 (ISSN 0920-2900), the biweekly publication of the Academic Hospital and Leiden Medical Faculty | 20240912_3 • michelvanderburg•com | Download PDF article below : file 20240912_3_CICERO
4) Onno R. Guicherit. Long-term metabolic sequelae of beta cell mass reduction, systemic venous drainage and denervation of the canine pancreas : experimental studies in relation to clinical pancreas transplantation. (Doctoral Thesis, Faculty of Medicine, Leiden University Medical Center (LUMC) , Leiden University)(S.l.: s.n.), (ISBN print: 9789090072319, 9090072314), 1994: 149 p. URL WorldCat https://search.worldcat.org/en/title/69433794
5) 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. URL Thesis Repository Leiden University https://hdl.handle.net/1887/3486604
9) Pancreatic Islet Transplantation • Isolation & Transplantation of Islets of Langerhans 1988 to early 1990s • Islet Transplant Laboratory • Leiden University Hospital • 20240912_1 • michelvanderburg•com | TakeNode 5b5ca362-2adf-497a-b2be-a83e47617017 |
Captions Image 20240912_1 :
1. Paul Langerhans
2. Section of the normal dog pancreas showing islets stained reddish-brown (immunostained for insulin)
3. Michel van der Burg, watching the dog islet isolation procedure in the Minneapolis surgical research laboratory (University of Minnesota), September 1989, with Philippe Morel and Pericles Tzardis
4. Experimental Surgery Laboratory in Leiden, June 1988, with (left to right) Hein Gooszen, Jane Field (Minneapolis), and Onno Guicherit, starting the surgical procedure for canine islet isolation
5. The pancreas (segment) is removed
6. Islet Transplant Laboratory in Leiden, at the start of islet isolation, with infusion of the collagenase solution via the ducts in the dog pancreas (whole gland for islet transplantation) – collagenase leaking from the pancreas is recirculated using a roller pump
7. During collagenase digestion at 37-39°C the pancreas falls apart, shown here in a low magnification microscopy image of pancreatic exocrine tissue, and a free-ed small blood vessel
8. Dissociated pancreatic tissue, on ice
9. Tissue is further dispersed in the cold isolation solution (here RPMI tissue culture solution is used), by aspiration in a syringe, and sieved to remove undigested fragments, ducts and vessels ~ demonstrated here by Jane Field (Minneapolis), with the introduction of the Minneapolis isolation procedure, June 1988, in our Islet Transplant Laboratory in Leiden
10. Microscopy of tissue suspension, with a low purity of the islets (stained red by dithizone) obtained by density separation in Dextran gradients (in Hanks’ solution) after islet isolation in the RPMI tissue culture solution (dark-brown exocrine fragments remain unstained)
11. Pure islet suspension obtained by density separation in Percoll gradients (in University of Wisconsin solution) after islet isolation in the University of Wisconsin solution (islets are only slightly stained due to poor diffusion over the cell membrane in the preservation solution)
12. Section of highly purified islets obtained by Dextran density separation after isolation in the University of Wisconsin solution
13. Islets are autotransplanted by infusion in the spleen of the dog
14. Transplanted islet in section of the spleen of one of the dogs shortly after the onset of fasting hyperglycemia at three months posttransplant (immunostained for insulin), 1989
15. Highly purified human islets obtained by Percoll density separation after isolation in the University of Wisconsin solution (immunostained with gold for insulin; not counterstained), July 1990
Pancreatic islet transplantation • Michel van der Burg • Miracles.Media | QR code (link to Thesis Repository Leiden University) https://hdl.handle.net/1887/3486604
Citation info : Pancreas & Islet Transplantation Program • 20240912 | Michel van der Burg | michelvanderburg•com
“Breakthrough in research into treatment of diabetics. Discovery by doctors of Leiden University Hospital” …headlines the Dutch newspaper ‘Leidsch Dagblad’ (1).
The dutch newspaper ‘Leidsch Dagblad’ reports October 24, 1989, on a breakthrough in the treatment of diabetic patients…successful transplantation of the insulin producing ‘islets’ in dogs, after isolation of the islets using the UW organ storage solution .
The first successful transplant June 13, 1989 was a big step. Generally multiple pancreases are needed for an adequate number of purified islets for one transplant. Here the dog’s pancreas was used for the isolation of islets, that were injected back in the animals’ spleen.
‘The breakthrough in the research came when Van der Burg came up with the idea of using the UW organ storage solution ( UWS ) — developed several years ago at the University of Wisconsin — for the preservation of the islets. This turned out to yield good results. The yield of pure islets could be increased using this method.’
Cicero
News based on story published Sep. 15th, 1989 by journalist Sylvia Van Leeuwen in Cicero, the biweekly publication of the Academic Hospital and Leiden Medical Faculty (2).
Ploeg, Gooszen and Van der Burg (left to right) discuss the achieved results, Monday Sep 4, 1989 at the Department of Surgery, University Hospital Leiden. Photo Tejo Ringers • 20240830_2 • michelvanderburg•com • TakeNode 3fc69a06-04bf-4f0d-bc77-cedb6d7b7f75
One more thing
We reported long-term function of the islet transplants (3,4). Failure after 3.5 years of a well-functioning islet transplant is puzzling. Nowadays, in clinical islet transplantation, failure of long-term functioning grafts in diabetic patients is still puzzling. Therefore, note (data not published before), that body weight of this autografted animal had increased to almost 150%, from 12.5 kg at the time of islet transplantation, to 18.0 kg at the time of graft failure 3.5 years later (Dec. 1992) — obviously, with an increased insulin demand that may have contributed to graft failure.
Notes
1) 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, URL https://leiden.courant.nu/issue/LD/1989-10-24/edition/0/page/15
The background in the image here (20240830_1), is the original color slide of the ‘Islets of Langerhans’ showing in the newspaper.
2) ‘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 | Download PDF article below : file 20240830_3_CICERO
4) Van der Burg MPM, Guicherit OR, Jansen JBMJ, Frölich M, Lamers CBHW, Lemkes HHPJ, Bruijn JA, Gooszen HG. Function and survival of intrasplenic islet autografts in dogs. Diabetologia 39, 37–44 (1996). https://doi.org/10.1007/BF00400411
5) 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.
6) The islet transplant news was first reported by me at an invited lecture July 8, 1989 for the Anglo Danish Dutch Diabetes Group meeting in St Edmund Hall, University of Oxford, Oxford (UK) : 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.
7) Leiden Islet Laboratory History • 20240803 | Michel van der Burg | michelvanderburg•com
Citation info : Islet Transplantation Breakthrough in Leiden University Hospital • 20240830 • Michel van der Burg • michelvanderburg•com
Pittsburgh (USA) May 31–June 3, 1992. Founding meeting, and 1st Int. Congress of the Cell Transplant Society.
Michel van der Burg, Co-chair ‘Methods’ Poster Discussion CTS , Pittsburgh June 3, 1992 • 20240812_2 • michelvanderburg•com • TakeNode 509ce973-d218-4f9c-84ef-ffa7c4fdb0d1
Poster creation
The poster was designed and produced May 1992 on a Macintosh computer using MacDraw II (with bar graphs from Cricket Graph) and printed landscape across a chain of several sheets of paper using the Imagewriter dotmatrix printer.
For this 2024 remastered poster below, the 1992 MacDraw II file was converted and edited using LibreOffice Vanilla, and next Pixelmator Pro was used for additional ‘repair’ (conversion issues with the many layers used for ‘tubes’ creation) and the insertion of the photo scans.
Van der Burg MPM, Guicherit OR, Scherft JP, Bruijn JA, Frölich M, Gooszen HG. Islet preservation during isolation: a new concept in cell transplantation. First International Congress of the Cell Transplant Society, Pittsburgh (USA) May 31 – June 3, 1992.
Van der Burg MPM, Guicherit OR, Frölich M, Bruijn JA, Gooszen HG. Islet preservation during isolation: a new concept in cell transplantation. Transplant Proc. 1992 Dec;24(6):2840-1. PMID: 1465965. PDF available below PMID_1465965 🔗
Update dd 20250115 – proceedings paper PMID: 1465965 added
Citation info : Pittsburgh 1992 Cell Transplant Society • 20240812 • Michel van der Burg • michelvanderburg•com
