Quantification of canine pancreatic islet isolation • 1st IPITA 1988 • @1MEMO 20251206

Quantification of canine pancreatic islet isolation • 1st IPITA , Stockholm (Sweden) March 27–29 1988 • Digitally remastered by author, publisher, Michel van der Burg • Miracles•Media • 1MEMO_20251206_01 • TakeNode 430989b2-52f0-4e36-8dbd-cf7bf030668c • #IEQ #diabetes #islets #transplant #methods #LUMC #IPITA

After founding the Leiden Islet Laboratory (1) in the University Hospital Leiden in Holland (later known as LUMC), and reporting the outcome of our first year of canine islet research at a national meeting November 1987 (2), next, this first poster ‘Quantification of canine pancreatic islet isolation’ for a world congress was presented March 1988 at the First International Congress on Pancreatic and Islet Transplantation (IPITA)* in Stockholm, Sweden (3,4).

This pilot work introduced our novel approach of volume quantification of islet isolation outcome by measuring the volume of the isolated islets . In addition we compared the outcome with the total volume of islets measured in the canine pancreas.
Note, that a similar approach, using islet volume measurements for the quantification in islet isolation assessment in man and large animals, was proposed the next year in an International Workshop during the 2nd Congress on Pancreas and Islet Transplantation, Sep. 1989, in Minneapolis, by Camillo Ricordi and some 150 participants from 30 institutes actively involved in islet isolation and transplantation — proposing a procedure for standardized islet volume measurements (based on the number of islets in diameter classes incrementing 50 µm) and reporting outcome in Equivalent Islet Numbers (total volume expressed in the equivalent number of spheres with a 150 µm diameter; abbreviated as EIN, currently known as the number of IEQs (Islet EQuivalents), which greatly enhanced islet research (5).

Unfortunately back problems prevented me to attend that 1st IPITA congress, I was looking forward to, but, fortunately, the poster was presented by my colleagues Hein Gooszen (Surgery Department) and Marijke Frölich (Chemical Pathology Department) of the University Hospital Leiden. Ms. Marijke Frölich also presented a nice poster (7,8) on our quantification of the islets cells , the hormones, in the right lobe (aka , the duodenal segment , the ventral lobe) and left lobe of the canine pancreas (aka, the body and distal tail , the dorsal lobe) of the beagle pancreas , showing the diversity of the islets in these two segments of the pancreas — corresponding to the head and tail of the human pancreas, respectively.
Below the excellent airbrush work by an artist from the Audiovisual Services of Leiden University, for our poster ‘Distribution of insulin, glucagon, pancreatic polypeptide and somatostatin in the canine pancreas’.

Airbrush art on poster board created by the Audiovisual Services of Leiden University. Showing the location of pancreatic tissue sampled from the proximal and distal part of the right and left lobe of the beagle pancreas. The hormone values did not differ significantly between the proximal and distal parts of each lobe. Michel van der Burg • Miracles•Media • 1MEMO_20251206_02 • TakeNode 10b1d696-9d7f-4fa3-a8f9-7a3211546f24

Poster board showing the distribution of the four different types of islet cells by assessment of the hormones insulin, glucagon, pancreatic polypeptide, and somatostatin between the right lobe (RL) and left lobe (LL) of the canine pancreas. The number of insulin, glucagon, and PP producing islet cells differs considerably between both lobes. Michel van der Burg • Miracles•Media • 1MEMO_20251206_03 • TakeNode 47333616-b85d-404e-b103-2ccb3b86d406

I created the original 1988 poster ‘Quantification of canine pancreatic islet isolation’ on March 9-10, 1988 using MacDraw on a personal Macintosh ED , using the bold Chicago font, and the Imagewriter-II matrix printer , except for the header provided by my colleagues , which was together with my colleagues’ posters designed and produced as usual at the time on rigid foam boards by the Audiovisual Services department of the Leiden University. Also the original photo print was pinned on the mounted poster (thus, not digitally processed at the time).
This digital remastered 2025 edition (1MEMO_20251206_1) was produced in LibreOffice Vanilla with conversion of the original 1988 MacDraw file, correcting the disrupted formatting, replacing the non-available Chicago font with the font ‘Chalkboard’ , adding a scan of the Figure 1 photo print , plus a recent photo taken of the original poster board, archived, header. Figure 1 uses a copy of that original photo print , with the addition now, in this remastered edition, of arrows helping identifying the islets , and addition of the text ‘(arrrows)’ in the figure legend.

Other papers presented at the 1st IPITA congress from our research group, on pancreas transplantation, are listed below (9,10,11,12).

David Sutherland

Several other centers reported at this 1st IPITA on succesful islet autotransplantation in large animals, including a series of presentations on canine islet transplantation from David Sutherland’s islet research group in Minneapolis.

We had already started collaborating, by the end of 1987, with David Sutherland and Ms. Jane Field , the head of Sutherland’s islet research laboratory in Minneapolis , planning Jane’s working visit for June 1988 in our Leiden Islet Laboratory, in order to help me set up in Leiden, the current Minneapolis procedure for canine islet isolation and transplantation (13,14).

The next year, Sep-Oct 1989, I worked again with Jane Field and David Sutherland, now in Minneapolis (14,15,16) in the islet research laboratory mostly, and also observing David Sutherland at work during clinical segmental pancreas autotransplantaton, where I made this portrait photograph (1MEMO_20251206_06).

David Sutherland • Clinical Pancreas Transplant, Minneapolis, 1989 • Michel van der Burg • Miracles.Media • 1MEMO_20251206_06 • TakeNode f4769bdf-c7a8-436a-bc5c-2d1505226c05 • David Sutherland performing a clinical segmental pancreas autotransplantation, Minneapolis, 1989. Photo by Michel van der Burg . URL https://michelvanderburg.com/2025/12/06

David Sutherland, the ‘father’ of pancreas and islet transplantation, passed away March 25, 2025.

David jokingly called the pancreas the “Big Dirty Island”.

Notes

* The founding meeting of the IPITA was being held actually at the 4th IPITA meeting — the 4th International Congress on Pancreas and Islet Transplantation — June 27–30, 1993 in Amsterdam (The Netherlands) hosted by Dr. Reinout van Schilfgaarde.

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

2. Cradle of Islet Transplants • 20240829 • Michel van der Burg • michelvanderburg•com • https://michelvanderburg.com/2024/08/29/cradle-of-islet-transplants-20240829/

3. Van der Burg MPM, Gooszen HG, Terpstra JL, Frölich M, Scherft JP, Lemkes HHPJ. Quantification of canine pancreatic islet isolation. First International Congress on Pancreatic and Islet Transplantation, Stockholm (Sweden) March 27–29, 1988. (Poster). Remastered 2025 poster edition : 1MEMO_20251206_01.

4. Van der Burg MPM, Gooszen HG, Terpstra JL, Frölich M, Scherft JP, Lemkes HHPJ. Quantification of canine pancreatic islet isolation (Abstract). Diabetes 1989; 38 (Suppl. 1): 274. (Abstract). View/Download file 1MEMO_20251206_04

1MEMO_20251206_04 Download

5. Quantitative And Qualitative Standards For Islet Isolation Assessment In Man And Large Mammals. International Workshop during the 2nd Congress on Pancreas and Islet Transplantation. Camillo Ricordi. Archive Michel van der Burg • Miracles•Media • 1MEMO_20251206_07 • TakeNode 3d90aa54-9fe1-4b29-8161-aa6c4fda6652 • View/Download file 1MEMO_20251206_07

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6. Ricordi C, Gray DW, Hering BJ, Kaufman DB, Warnock GL, Kneteman NM, Lake SP, London NJ, Socci C, Alejandro R, et al. Islet isolation assessment in man and large animals. Acta Diabetol Lat. 1990 Jul-Sep;27(3):185-95. doi: 10.1007/BF02581331. PMID: 2075782.

7. Frölich M, Van der Burg MPM, Gooszen HG, Jansen JBMJ, Lamers CBHW. Distribution of insulin, glucagon, pancreatic polypeptide and somatostatin in the canine pancreas. First International Congress on Pancreatic and Islet Transplantation, Stockholm, Sweden, March 27–29 1988. (Poster).

8. Frölich M, Van der Burg MPM, Gooszen HG, Jansen JBMJ, Lamers CBHW. Distribution of insulin, glucagon, pancreatic polypeptide, and somatostatin in canine pancreas (Abstract). Diabetes 1989; 38 (Suppl. 1): 257. (Abstract) . Download file 1MEMO_20251206_04

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9. Gooszen HG, Van der Burg MPM, Guicherit OR, Jansen JBMJ, Van Schilfgaarde R, Lamers CBHW, Frölich M. A crossover study on the effects of duct obliteration, coeliac denervation and autotransplantation on glucose and meal stimulated insulin, glucagon and pancreatic polypeptide levels. First International Congress on Pancreatic and Islet Transplantation, Stockholm, Sweden, March 27–29 1988. (Talk).

10. Gooszen HG, van der Burg MP, Guicherit OR, Jansen JB, Frölich M, van Schilfgaarde R, Lamers CB. Crossover study on effects of duct obliteration, celiac denervation, and autotransplantation on glucose- and meal-stimulated insulin, glucagon, and pancreatic polypeptide levels. Diabetes. 1989 Jan;38 Suppl 1:114-6. doi: 10.2337/diab.38.1.s114. PMID: 2642831. (Proceedings paper).

11. Gooszen HG, Van Schilfgaarde R, Van der Burg MPM, van Lawick van Pabst WP, Frölich M, Bosman FT. Quantitative assessment of changes in insulin secretion after canine ductobliterated segmental pancreatic autotransplantation in relation to the histological background. First International Congress on Pancreatic and Islet Transplantation, Stockholm, Sweden, March 27–29 1988. (Poster).

12. Gooszen HG, Van Schilfgaarde R, Van der Burg MPM, Van Lawick van Pabst WP, Frölich M, Bosman FT. Quantitative assessment of changes in insulin secretion after canine duct-obliterated segmental-pancreas autotransplantation in relation to histological background (Abstract). Diabetes 1989; 38 (Suppl. 1): 255–256. (Abstract). View/Download file 1MEMO_20251206_05

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13. December 1987 , we started planning together Jane Field’s working visit thanks to our nephrologist Fokko van der Woude who after post doc research in Minneapolis had just started as an associate Professor at the Leiden University , working in our Leiden University Hospital (LUMC). Fokko J. van der Woude (1953-2006) passed away too soon after a long battle with cancer.

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

15. Visiting research fellow in the Department of Surgery at the University of Minnesota (DER Sutherland, MD PhD) & Department of Cell Biology (OD Hegre, MD PhD), University of Minnesota, Minneapolis Minnesota (USA) , September 14-October 6 1989

16. 2nd International Congress on Pancreatic and Islet Transplantation, and 4th International Symposium on Organ Procurement and Preservation. Minneapolis (USA) September 17–22, 1989.

Citation info : Quantification of canine pancreatic islet isolation • 1st IPITA 1988 • Michel van der Burg • Miracles.Media • @1MEMO 20251206 • URL https://michelvanderburg.com/2025/12/06

Pancreas & Islet Transplantation Program • 20240912

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).

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).

Monitoring insulin secretion by pancreatic islets in perifusion • 20240911 • Michel van der Burg • michelvanderburg•com | URL https://michelvanderburg.com/2024/09/11/monitoring-pancreatic-islets-in-perifusion-20240911/

Minneapolis method

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

20240912_3_CICERO Download

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

6) Monitoring pancreatic islets in perifusion • 20240911 • Michel van der Burg • michelvanderburg•com | URL https://michelvanderburg.com/2024/09/11/monitoring-pancreatic-islets-in-perifusion-20240911/

7) Minneapolis 1989 Poster | 20240804 | Michel van der Burg | michelvanderburg•com | URL https://michelvanderburg.com/2024/08/04/minneapolis-1989-poster-20240804/

8) 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/

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

Minneapolis 1989 Poster | 20240804

September 1989 at a symposium of two international societies in Minneapolis, USA (1) , I presented this first poster on the ‘ invention ‘ of using the UW solution ( the University of Wisconsin organ preservation solution) during pancreatic islet isolation, with the exciting discovery of near-complete purification of islets of Langerhans in the laboratory for transplantation in diabetic patients.

Here the remastered 20240804 edition of that Minneapolis 1989 poster presentation.

A previous edition of the remastered poster was published here two years ago (2) but that edition had a different photo print (higher magnification, and without the bar indicator) of the purified islet preparation inserted, not the original image. This has been corrected now. In addition the original line spacing is now restored.

Notes

1) 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.

2) Minneapolis 1989 Poster UW Solution Islet Isolation | 20220822 | Michel van der Burg | michelvanderburg•com | URL https://michelvanderburg.com/2022/08/22

Updates

20241211 : Minor text updates

Citation info : Minneapolis 1989 Poster | 20240804 | Michel van der Burg | michelvanderburg•com | TakeNode 91d70715-3fb3-4380-906a-0daf1b5ddd6a

Lancet Letter 1989 UW Solution Islet Isolation | 20220823

Lancet Letter 1989 UW Solution Islet Isolation | 20220823 | Michel van der Burg | michelvanderburg•com | June 1989 preparing first submission for publication as letter in the Lancet medical journal the new concept of using the UW solution ( the University of Wisconsin organ preservation solution) for isolation and complete purification of islets of Langerhans in the laboratory for transplantation in diabetic patients. Later that year that exciting discovery was presented at meetings in Minneapolis, USA, and Barcelona, Spain. Details in yesterday’s post. Submission for publication as a letter in the Lancet had had no succes 😉
Final draft text produced on my personal Macintosh ED and Imagewriter-II matrix printer with Geneva font.

TakeNode ID: 9f11f523-9b5f-47e8-be99-b242a1ba9b40

TAGS #Lancet #journal #UWS #UW #solution #preservation #organ #islet #isletofLangerhans #Langerhans #pancreas #poster #concept #purification #transplantation #congress #meeting #Minneapolis #Netherlands #Leiden #LUMC #AZL #Barcelona #Spain #LibreOffice #Vanilla #MacDraw #MacintoshED #512K #Imagewriter #TakeNode #1Memo #michelvanderburg

Minneapolis 1989 Poster UW Solution Islet Isolation | 20220822

The next month at a meeting in Barcelona, Spain, this rather radical new concept was introduced (2, 3). June 1989 submission for publication as a letter in the Lancet had had no succes 😉

Poster designed and produced on my personal Macintosh ED and Imagewriter-II matrix printer, allowing full width printing over multiple pages in landscape (a low cost do-it-yourself discovery by me, at a time when posters were prepared on poster boards by graphical professionals using photography and special lettering techniques for around $400). Original MacDraw II file conversion with LibreOffice Vanilla.

Notes

2) 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.

3) 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; 22: 2050–2051.

Updates

20240804 – This remastered 20240804 edition of the Minneapolis 1989 poster , now shows the original photo of the islet prep as posted at the meeting in 1989. In addition the correct line spacing is now restored.
The previous poster published online two years ago (20220822) showed a different photo print (higher magnification, and without the bar indicator) of the same islet prep, not the correct image.

20241211 – Minor text updates

Citation info : Minneapolis 1989 Poster UW Solution Islet Isolation | 20220822 | Michel van der Burg | michelvanderburg•com | TakeNode 91d70715-3fb3-4380-906a-0daf1b5ddd6a