Tag: surgery

Dutch Islets Transplant Team • @1MEMO 20250125

Islets isolated April 18, 1989 using the UW-Solution • Miracles.Media • 20250103_1 • TakeNode eeb55729-c02b-4f73-ab0e-9f71b65bf85e

Rightaway, April 1989, when we obtained these highly purified canine islets of Langerhans by introducing the UW-Solution for isolating the islets from pancreases (1,2,3), we started using these islets to study the importance of gut factors for islet transplants — the capacity of the isolated islets to secrete insulin during stimulation with glucose, other nutrients, and potentially gut hormones ( ‘incretins’).

Isolated islets in perifusion chambers

Isolated islets, not transplanted, were examined in the Leiden Islet Laboratory. The insulin secretion of these islets was measured, while the islets were housed in plastic micro-chambers , that were flushed with solutions containing various levels of glucose and gut hormones , mimicking the blood levels as found following meals in islet transplants (4).

Monitoring pancreatic islets in perifusion • Michel van der Burg • Miracles.Media • @1MEMO 20240911

Autotransplantation of islets

A few months later , Summer 1989, we performed a series of transplants of isolated canine islets (5) , we likewise focussed our research on the importance of gut factors in metabolic control by the islet grafts, and therefore introduced meal tests — apart from a series of intravenous tests. Both simple and convenient, such meal tests proofed to be also an excellent way to study both the capacity of the transplanted islets to secrete insulin, as well as the contribution of gut hormones – in the so-called ‘entero-insular axis’ (6).

Autotransplantation of islets in the spleen • Michel van der Burg • Miracles.Media • @1MEMO 20250125_1 • Left : Canine pancreas with two cannulas in the pancreatic ducts (for infusion of collagenase solution) , with the blood vessels clamped at the time of removal of the gland. Not shown here: After removal of the gland the collagenase solution is infused , and the pancreatic islets are isolated within a few hours. Right : Next the purified islets are returned by infusion in the spleen of the same animal (auto-transplantation). Drawings by medical artist J. Wetselaar-Whittaker — with my hand posing for the injection drawing ;)

Contribution of gut factors to canine isolated islet function ?

Spring 1990 our first results could be presented of these sophisticated islet function tests upto 3 months after islet transplantation, together with our first findings of the direct effects of the gut hormones CCK and GIP on the isolated islets in the perifusion system in the Leiden Islet Lab.

Spring meeting 1990 of the Dutch Society for Gastroenterology, Veldhoven, Netherlands • Michel van der Burg • Miracles.Media • @1MEMO 20250125_2

Here the proceedings presented at the 1990 spring meeting of the Dutch Society for Gastroenterology (7).

Dutch Islets Transplant Team

October 8, 1990, Paul van Suylichem, from the Groningen islet research group, visited his alma mater again, the Leiden University on the occasion of the 3rd Symposium Experimental Surgical Research (SEOHS).
I was presenting results at the symposium on metabolic control upto 3 mo after the succesful canine islet transplants – islets isolated using the UW-Solution – known as Viaspan for the cold storage of donor organs (8,9).
Paul had started together with me in 1985 building the Leiden Islet Lab (10), that I continued from 1986 after Paul left together with project leader Reinout van Schilfgaarde starting the Groningen islet group (11).
I took the chance to invite Paul for a visit together that day in the nearby Leiden Islet Lab , for a closer look at our latest work on canine islet isolation, transplantation, and the new Percoll-UWS purification gradients (12) — and took this picture of Paul examining an islet prep at the microscope in the lab , with the Acusyst perifusion system in the background.
In late 1990, the Groningen islet team with Paul would also start this preclinical model of canine islet isolation and transplantation.

Paul van Suylichem (Groningen Islet Team) in Leiden Islet Laboratory, October 8, 1990 • Photo by Michel van der Burg • Miracles.Media • @1MEMO 20250125_3

A year later, Oct 1991, during the 5th Congress of the European Society for Organ Transplantation Congress (5th ESOT) in Maastricht (12), I learned from Paul’s co-worker Jan-Erik van Deijnen that the Groningen team, after initially several failed transplant attempts, had finally succeeded in the last 5 transplants in a row. They had mastered the technique and had started to complete this work with histology of the transplants.

We, in Leiden, had made plans earlier that summer to expand our small group of islet transplants, with a second series of transplants with a view to expanding our research on metabolic control in islet transplantation, with new sophisticated research on the effect on insulin secretion of the newly discovered gut hormone GLP-1. At the same time we would also be able to test our efficient new technique of isolation and purification of the islets in that transplantation setting.

A few days after this 5th ESOT congress it seemed better to me to refrain from new transplants in more animals, and I proposed to expand our sophisticated, functional research with research on the Groningen canine islet transplants.

Later that month, Oct 1991, islet perifusion experiments with the gut hormone GLP-1 were started (13,14,15).

And… November 1991, Paul van Suylichem’s research associate Annemiek Weemaes brought the Groningen canine transplants to Leiden, for our very successful collaborative project , with the planned additional studies in the combined Leiden and Groningen group of transplants, examining additionally insulin action (sensitivity) and the ‘incretin’ effect (stimulation of insulin secretion) of the gut hormone GLP-1. Experiments we completed in 1992 (14,16,17,18).

Notes

IMAGE 20250103_1
Islets isolated April 18, 1989 using the UW-Solution • Miracles.Media • 20250103_1 • TakeNode eeb55729-c02b-4f73-ab0e-9f71b65bf85e

1) Pancreatic Islet Isolation With UW Solution • A New Concept • Michel van der Burg • Miracles.Media • @1MEMO 20241224 • URL https://michelvanderburg.com/2024/12/24/pancreatic-islet-isolation-with-uw-solution-a-new-concept-20241224/

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) Pancreatic Islets UWS Series 1989 • Kodak PhotoCD • Michel van der Burg • Miracles.Media • @1MEMO 20250103 • URL michelvanderburg.com/2025/01/03/

4) Monitoring pancreatic islets in perifusion • Michel van der Burg • Miracles.Media • @1MEMO 20240911 • TakeNode fdf6f65c-28b7-4936-8c23-83225e6f2ff0 • URL https://michelvanderburg.com/2024/09/11/

IMAGE 20240911
Monitoring pancreatic islets in perifusion • Michel van der Burg • Miracles.Media • @1MEMO 20240911 • TakeNode fdf6f65c-28b7-4936-8c23-83225e6f2ff0

5) Islet Transplantation Breakthrough in Leiden University Hospital • 20240830 • Michel van der Burg • michelvanderburg•com • URL https://michelvanderburg.com/2024/08/30/

6) Entero Insular Axis • Michel van der Burg • Miracles.Media • @1MEMO 20250123 • URL michelvanderburg.com/2025/01/23/

IMAGE 20250125_1
Autotransplantation of islets in the spleen • Michel van der Burg • Miracles.Media • @1MEMO 20250125_1 • Left : Canine pancreas with two cannulas in the pancreatic ducts (for infusion of collagenase solution) , with the blood vessels clamped at the time of removal of the gland. Not shown here : After removal of the gland the collagenase solution is infused , and the pancreatic islets are isolated within a few hours. Right : Next the purified islets are returned by infusion in the spleen of the same animal (auto-transplantation). Drawings by medical artist J. Wetselaar-Whittaker — with my hand posing for the injection drawing ;) • TakeNode da74e6a2-e21d-4690-afe5-356949221658

IMAGE 20250125_2
Spring meeting 1990 of the Dutch Society for Gastroenterology, Veldhoven, Netherlands • Michel van der Burg • Miracles.Media • @1MEMO 20250125_2 • TakeNode 65cb9de6-a111-4636-8766-d586b001d73e

7) Van der Burg MPM, Guicherit OR, Jansen JBMJ, Lamers CBHW, Scherft JP, Gooszen HG.
Contribution of gut factors to canine isolated islet function? Spring meeting of the Dutch Society for Gastroenterology (NVGE), Veldhoven (The Netherlands) March 23–24, 1990. The proceedings pdf (1MEMO_20250125_2) is available for download below.

1MEMO_20250125_2🔗Download

Five years later the Dutch Society for Gastroenterology awarded the Glaxo Wellcome Gastrointestinal Research Award for this research (Ph.D. thesis “Pancreatic islet transplantation”) at the Fall meeting of the Dutch Society for Gastroenterology (NVGE), Veldhoven, The Netherlands, October 5, 1995).

Glaxo Wellcome Gastroenterology Research Award, Oct 5, 1995, Dutch Society for Gastroenterology, Veldhoven, Netherlands • Michel van der Burg • Miracles.Media • @1MEMO 20250125_4 • TakeNode 3152bca6-c98e-4900-89bf-d3e241f14405

8) Van der Burg MPM, Guicherit OR, Ploeg RJ, Scherft JP, Bruijn JA, Frölich M, Prins FA, Gooszen HG. Successful canine pancreatic islet transplantation using ViaSpan. 3rd Symposium Experimental Surgical Research (SEOHS), Leiden (The Netherlands) October 8, 1990.

9) Van der Burg MPM, Gooszen HG, Ploeg RJ, Guicherit OR, Scherft JP, Terpstra JL, Frölich M. Over 90% purified canine isolated pancreatic islets using UW solution (Abstract). Neth J Surg 1990; 42: 30. Pdf abstract (1MEMO_20250125_5) is available for download below.

1MEMO_20250125_5🔗Download

10) Leiden Islet Laboratory History • 20240803 | Michel van der Burg | URL michelvanderburg.com/2024/08/03/

11) Cradle of Islet Transplants • 20240829 • Michel van der Burg • URL https://michelvanderburg.com/2024/08/29/

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

IMAGE 20250125_3
Paul van Suylichem (Groningen Islet Team) in Leiden Islet Laboratory, October 8, 1990 • Photo by Michel van der Burg • Miracles.Media • @1MEMO 20250125_3 • TakeNode e8ce7630-4e75-402b-a4c2-9b007a8dd61b

13) Van der Burg MPM, Guicherit OR, Scherft JP, Frölich M, Terpstra JL, Gooszen HG. Functie na intralienale transplantatie van eilandjes van Langerhans in de hond ( Function after intrasplenic transplantation of islets of Langerhans in dogs ). Surgeon days ’92 of the Dutch Surgery Society, Rotterdam (The Netherlands) May 21–22, 1992. In : Gut factors controlling pancreatic islets • 20240910 | Michel van der Burg | michelvanderburg•com

14) 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

15) van der Burg MPM, Guicherit OR, Frölich M, Gooszen HG. Insulinotropic effects of cholecystokinin, gastric inhibitory polypeptide and glucagon-like peptide-1 during perifusion of short-term cultured canine isolated islets. Regul Pept. 1995 Dec 7;60(1):61-7. doi: 10.1016/0167-0115(95)00122-4. PMID: 8747785.

16) Van der Burg MPM, Van Suylichem PTR, Guicherit OR, Frölich M, Lemkes HHPJ, Gooszen HG. Glycemic control mechanisms after canine islet autografting. 5th International Congress on Pancreas and Islet Transplantation (IPITA), Miami Beach (USA) June 18–22, 1995.

17) van der Burg MPM, van Suylichem PTR, Guicherit OR, Frölich M, Lemkes HHPJ, Gooszen HG. Glycemic control mechanisms after canine islet autografting. Transplant Proc. 1995 Dec;27(6):3187-8. PMID: 8539903. Download (PMID_8539903) below .

PMID_8539903🔗Download

18) van der Burg MPM, van Suylichem PTR, Guicherit OR, Frölich M, Lemkes HHPJ, Gooszen HG. Glucoregulation after canine islet transplantation: contribution of insulin secretory capacity, insulin action, and the entero-insular axis. Cell Transplant. 1997 Sep-Oct;6(5):497-503. doi: 10.1177/096368979700600509. PMID: 9331501. Download Free PDF https://hdl.handle.net/11370/59231eab-6091-415d-8b2b-4e5e6508a978

Citation info : Dutch Islet Transplants Team • Michel van der Burg • Miracles.Media • @1MEMO 20250125 • URL michelvanderburg.com/2025/01/25/

No Title • @1MEMO 20250112

No Title • Oil- Acrylic painting by Hans Dudart • Miracles.Media • @1MEMO 20250112_1 • TakeNode cbd20789-ebf5-4ede-925b-9b861c6719a4

Scan of print (10×15 cm; photo G.J. v.d. Poort) of oil- acrylic painting (60x50cm) by Hans Dudart.

Hans Dudart (1955-2003) worked as an artist in Holland, and as a valued co-worker in our Experimental Surgical Laboratory of the Leiden University Hospital (AZL, now LUMC) in Leiden, Holland. He died too soon from type 1 diabetes.

Citation info : No Title • Michel van der Burg • Miracles.Media • @1MEMO 20250112 • URL michelvanderburg.com/2025/01/12/

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).


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).


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_CICERODownload

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

Islet Transplantation Breakthrough in Leiden University Hospital • 20240830

Breakthrough Islet Transplantation • 20240830_1 • michelvanderburg•com • TakeNode e12ae9d5-6a93-444f-b5e2-8c83434d7d6e

“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 (UWS)

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 — 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, file 20240830_3_CICERO

20240830_3_CICERODownload

3) Function and survival of intrasplenic islet autografts in dogs. In : Pancreatic islet transplantation (doctoral thesis, 1994) by Michel van der Burg. ISBN 9789080216402. Scholarly Publications repository of Leiden University. URL https://scholarlypublications.universiteitleiden.nl/access/item%3A3486614/view

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

Cradle of Islet Transplants • 20240829

Isolation of Islets of Langerhans from the Canine Pancreas | Fall meeting of the Dutch Association for Calcium and Bone Metabolism, Leiden (The Netherlands) November 13, 1987 • 20240829_1 • michelvanderburg•com • TakeNode 6b80e3a7-af16-41f7-b15f-cdeb85e377f3

Cradle of Islet Transplants

The Laboratory of Cell Biology and Histology in Leiden (headed by Prof J.P. Scherft), was the cradle of our Islet Transplantation Lab, where we made a fresh start Summer 1986 (1), and presented our first poster the following year.

Poster

Our first year of research was presented in this poster (Image 20240829_1) at the Fall Meeting Friday, November 13, 1987 , of the Dutch Association for Calcium- and Bone-metabolism*, in Leiden, Holland (2) in that Cell Biology building of the University Hospital Leiden (‘Building 55’) where our Islet Lab was hosted for the first decade.

The poster shows the results of islet isolations from canine pancreas segments performed with a method developed for human islet isolation by the surgeon Derek Gray (Oxford, UK) with some modifications (3). Pancreas segments were harvested at surgery for our concommitant research on segmental pancreas transplantation in this pre-clinical model (4,5,6,7).


Isolation of Islets of Langerhans from the Canine Pancreas | Islet Transplantation Laboratory, Leiden University Hospital, 1987 • 20240829_2 • michelvanderburg•com • TakeNode a9a389d9-c06f-467a-9ee0-1c2dc5f2403a

The photo collage (Image 20240829_2) also shown in the Methods section of the poster illustrates, resp. :
1) removal of a canine pancreatic segment at surgery;
2) distension of the gland by ductal injection of a collagenase solution;
3) the mucoid appearance after collagenase digestion of the connective tissue in the gland for 20-25 min at 39°C;
4) the digestion end-point, when gentle contusion of a sample of the tissue appears to liberate free islets from the surrounding exocrine tissue;
5) dispersion of the tissue with forceps and aspiration through needles;
6) microscopy of the suspension of purified islets (arrow denotes islet) contaminated with some exocine fragments , after sieving and Ficoll density gradient centrifugation to separate the islets from most of the exocrine fragments.

Figure 1 of the Results shows the relation between islet size and number of the isolated islets. Quantitation of the total volume of islets in the pancreas, and after islet isolation , demonstrated that on average 5-10% of the islets in the pancreas are isolated after purification. Figure 2 shows the timeline of insulin secretion by the isolated islets, in response to stimulation with glucose (sugar) during perifusion with a basic salts solution containing low -, high -, and low sugar levels, resp.


Posters Cell Biology, Leiden, Nov. 1987 • 20240829_3 • michelvanderburg•com • TakeNode 19d17e89-3138-4ef7-9490-6716f3994067

The posters were produced at the Cell Biology department using a pen plotter machine.
A corridor in the building with part of the gallery of posters was photographed at the meeting (Image 20240829_3).

Cell Biology – 40th anniversary, 1947-1987


Laboratory of Cell Biology and Histology, Leiden (Holland) celebrating the 40th anniversary, 1947-1987. Front entrance ‘Building 55’ University Hospital Leiden, November 14, 1987 20240829_4 • michelvanderburg•com • TakeNode bcf4674c-0cc7-4545-96b1-1a8e0c451150

The 40th anniversary of the Cell Biology Department was celebrated 13-14 November 1987 (with a banner and flags at the entrance of the building (Image 20240829_4) , with the science meeting Nov. 13th and a get-together with (former) co-workers, including Professor emiritus Pieter J. Gaillard, dutch pioneer of tissue culture and transplantation, and founder of the laboratory when appointed professor of Experimental Histology at the Leiden University, Friday, November 14, 1947 (8,9).

Professor Gaillard’s lab started in 1947 in the cellar of the Anatomical Laboratory, and moved in 1953-1954 to ‘Building 55’ of the University Hospital Leiden; shown above. The name was changed to Cell Biology and Histology, in 1964. Cell Biology is currently part of the Department Of Cell & Chemical Biology , and housed within the research building of the Leiden University Medical Centre.

I photographed the emiritus Gaillard receiving a ‘souvenir’ from Professor Scherft (Image 20240829_5) at the 40th anniversary of the Cell Biology Laboratory in Leiden (Holland), Nov. 14, 1987.


P.J. Gaillard (on the left) & J.P. Scherft, Cell Biology Laboratory in Leiden (Holland), Nov. 14, 1987 • 20240829_5 • michelvanderburg•com • TakeNode 08054d8f-c978-422f-9f3f-5c8507cf8869

First clinical islet cell transplant

In 1944, during World War II, Gaillard and the Leiden surgeon P.J. Kooreman performed the first successfull clinical (allogeneic) transplant of (cultured) islet cells in Leiden.
Dutch newspapers reported (10), Gaillard had spoken at a meeting in 1949 organized by local hospitals in The Hague, Holland, on some of his early transplants in diabetic patients, with success in one patient during the war (Image 20240829_6) :
“Prof. Gaillard considers it too early to say much about the possibilities of this intervention. Although he could report that a female patient can be considered cured in nine months. A bombing took her life, so that further observation was cut off.” .
The Islet Transplant Registry listed the transplant as the 5th performed in the world (6).
Gaillard & Kooreman also performed a successful series of transplants of cultured parathyroid tissue , a firm base of what would become the focus of Gaillards research and the Cell Biology Laboratory , the hormonal regulation of bone metabolism (9,10,11,12).


Prof. Dr. P.J. Gaillard spoke about successes in transplant trials. Nieuwe Leidsche Courant, Oct. 1, 1949 • 20240829_6 • michelvanderburg•com • TakeNode c5be6800-f3da-453e-9d40-d8fafffd27aa

Introduction of collagenase isolation of islets

Also, of note, is the first introduction of pancreatic islet isolation by collagenase digestion in 1965 by the polish researcher Stanislaw Moskalewski with the help of Gaillard working at the Cell Biology Laboratory (13) — the basis of large scale islet isolation and transplantation.

Notes

1) Leiden Islet Laboratory History • 20240803 | Michel van der Burg | michelvanderburg•com

2) Van der Burg MPM, Gooszen HG, Terpstra JL, Scherft JP, Frölich M, Lemkes HHPJ. Isolation of the islets of Langerhans from the canine pancreas. Fall meeting of the Dutch Association for Calcium and Bone Metabolism, Leiden (The Netherlands) November 13, 1987.

3) Gray DWR, McShane P, Grant A, Morris PJ. A Method for Isolation of Islets of Langerhans from the Human Pancreas. Diabetes 1 November 1984; 33 (11): 1055–1061. https://doi.org/10.2337/diab.33.11.1055

4) Gooszen HG. Canine segmental pancreatic autotransplantation. Analysis of the effects of ductobliteration. Thesis, Leiden, 1984

5) Van der Burg MPM, Gooszen HG, Guicherit OR, Jansen JBMJ, Frölich M, Haastert FA, Lamers CBHW. Contribution of partial pancreatectomy, systemic hormone delivery and duct obliteration to glucose regulation in canine pancreas: Importance in pancreas transplantation. Diabetes 1989; 38: 1082–1089.

6) Pancreatic islet transplantation (doctoral thesis, 1994) by Michel van der Burg. ISBN 9789080216402. Scholarly Publications repository of Leiden University. Persistent URL https://hdl.handle.net/1887/3486604

7) Eerste alvleesklier-transplantatie | Nederlandse primeur in Academisch Ziekenhuis Leiden. In : Leidsch Dagblad, May 18, 1984 | Dutch newspaper , URL https://leiden.courant.nu/issue/LD/1984-05-18/edition/0/page/1


Eerste alvleesklier-transplantatie | Nederlandse primeur in Academisch Ziekenhuis Leiden. Leidsch Dagblad, May 18, 1984 (leiden.courant.nu) • 20240829_7 • michelvanderburg•com • TakeNode 5d3c88a5-4c67-48fd-8a8c-8165a5c2edfe

8) Van CH0 naar CH40 met Ca2+ als katalysator. Scherft J.P. In : Laboratorium voor Celbiologie en Histologie 1947-1987 | Uitgave ter gelegenheid van het veertigjarig bestaan van het Laboratorium voor Celbiologie en Histologie van de Medische Faculteit te Leiden.

9) Enkele notities over het begin van de weefselkweek in Leiden. Gaillard P.J. In : Laboratorium voor Celbiologie en Histologie 1947-1987 | Uitgave ter gelegenheid van het veertigjarig bestaan van het Laboratorium voor Celbiologie en Histologie van de Medische Faculteit te Leiden.

10) Prof. dr P.J. Gaillard sprak over successen bij transplantatie-proeven. Nieuwe Leidsche Courant, Oct. 1, 1949. | Dutch newspaper , URL https://leiden.courant.nu/issue/NLC/1949-10-01/edition/null/page/2 | “Prof. Gaillard acht het nog te vroeg om over de mogelijkheden van deze ingreep veel te zeggen. Al kon hij mededelen, dat een vrouwelijke patiënt in negen maanden tijds als genezen beschouwd kan worden. Een bombardement benam haar het leven, zodat men van verdere observatie werd afgesneden”.

On 10 and 11 December 1944, Leiden was bombed by English RAF aircraft. The bombings missed their target. Residential areas near Leiden railway stations were hit, resulting in many civilian casualties. Info from Erfgoed Leiden URL https://www.erfgoedleiden.nl/nieuws/vondst-van-de-week/1092-vvdw-bombardementen-op-leiden

11) Een totaal nieuw terrein voor de chirurgie. Prof. Kooreman inaugureerde in Leiden. In : Nieuwe Leidsche Courant 20 jun. 1959, p. 3 | Dutch newspaper , URL URL https://leiden.courant.nu/issue/NLC/1959-06-20/edition/0/page/3

12) Jon van Rood: The pioneer and his personal view on the early developments of HLA and immunogenetics. Martine J. Jagera M.J, Brand A, Claas F.H.J. Transplant Immunology 52 (2019) 1–26

13) Beginning of pancreatic islet isolation by collagenase digestion (personal reminiscences). Stanislaw Moskalewski. Ann Transplant 1997; 2(3): 6-7. URL https://annalsoftransplantation.com/abstract/index/idArt/647800

* Strange to find the Dutch Association for Calcium and Bone Metabolism indicates online a start in 1990 – while I visited their fall meeting in 1987 (see also refs 8,9)

Update (20240912) correction text perifusion solution

Citation info : Cradle of Islet Transplants • 20240829 • Michel van der Burg • michelvanderburg•com

Lucky #1 Islet • 20240811

Shortly after starting our Islet Lab end 1986, I hand-picked and photographed this special big heart-shaped isolated islet of Langerhans with Uncle Scrooge McDuck’s ‘lucky #1 dime’ in mind.
(dutch : Dagobert Duck’s geluksdubbeltje). This ‘First Islet’ poster was pinned to the wall in my study in the (small) Islet Lab ‘wing’ in the Cell Biology building of the Leiden University Hospital.

It’s an Islet of Langerhans isolated from a rat pancreas. For pilot work, the first months while developing our islet project plan, islets were isolated from rat pancreases.
I had started developing our basic lab methods… like eg. measuring the insulin secretion capacity and insulin content of isolated islets. A custom-made glass pipet was used to hand-pick and transfer the islets to little polypropyleen ‘Eppendorf’ tubes for insulin secretion tests with glucose stimulation.

Citation info : Lucky #1 Islet • 20240811 • Michel van der Burg • michelvanderburg•com | TakeNode 5234a6e0-4565-4167-bb46-0f922c0b1d2a

Organ Transplantation 1983 Symposium • 20240810

Friday, September 2, 1983 talk by Hein Gooszen, on experimental pancreas transplantation (1), at the International Symposium on Organ Transplantation in Diabetics (2) in the Hall of Knights (dutch : Ridderzaal), Binnenhof (English: Inner Court), The Hague, Netherlands.

Notes

1. Hein Gooszen, Reinout van Schilfgaarde, Marijke Frölich, Michel van der Burg (Leiden, The Netherlands). Long-term endocrine function of ductobliterated in situ and autografted left canine pancreatic segments. International Symposium on Organ Transplantation in Diabetics, The Hague, The Netherlands, September 1–2, 1983.

2. Reinout van Schilfgaarde (Leiden, The Netherlands) chaired the organizing and scientific committee.

Citation info : Organ Transplantation 1983 Symposium • 20240810 • Michel van der Burg • michelvanderburg•com • TakeNode (20240810_1) 37e1dc78-b59f-4305-8441-55f8d02cce6b • TakeNode (20240810_2) 57e8de9e-639b-422b-a567-bc1399dd1b4e