Optiprep For Human Islet Purification • Cell Transplant Society 1999 • @1MEMO 20250203

Optiprep For Human Islet Purification • Cell Transplant Society 1999 • Michel van der Burg • Miracles.Media • @1MEMO 20250203 • TakeNode bad757b8-674c-4371-938c-ac73287bc457

Poster (#57) presentation Michel van der Burg, Cell Transplant Society congress 1999 in Montreux, Switzerland (1,2)

Outcome of the first series of human islet purifications with the novel Iodixanol -UWS density gradient — developed in the Leiden Islet Laboratory of the LUMC — performed during my working visit April – May 1998 at the “fast track” center of the Diabetes Research Institute (Scientific director Prof. C. Ricordi, MD) of the University of Miami (Miami, FL, USA).

Notes

1) Van der Burg MPM, Ranuncoli A, Molano R, Kirlew T, Ringers J, Bouwman E, Terpstra OT, Ricordi C. Optiprep for human islet purification. 4th International congress of the Cell Transplant Society, Montreux (Switzerland) March 21–24, 1999 .

2) Van der Burg MPM, Ranuncoli A, Molano R, Kirlew T, Ringers J, Bouwman E, Terpstra OT, Ricordi C. Optiprep for human islet purification (Abstract). Cell Transplant 1999; 8: 184. Download abstract below 1MEMO_20250202_3

Citation info : Optiprep For Human Islet Purification • Cell Transplant Society 1999 • Michel van der Burg • Miracles.Media • @1MEMO 20250203 • URL michelvanderburg.com/2025/02/03/

Iodixanol-UWS Purification and Culture of Pig Islets Xeno Transplants • Cell Transplant Society 1999 • @1MEMO 20250202


Iodixanol-UWS Purification and Culture of Pig Islets Xeno Transplants • Cell Transplant Society 1999 • Michel van der Burg • Miracles.Media • @1MEMO 20250202

Slideshow (digitally remastered) oral presentation Michel van der Burg, Cell Transplant Society congress 1999 in Montreux, Switzerland (1)

The Leiden Islet Laboratory developed a novel Iodixanol-UWS density gradient for purification of the islets of Langerhans from the pancreas in the difficult pig model.

Pig islet isolation from the pancreas of slaughterhouse sows was markedly improved by keeping the islets in the UW donor organ preservation solution (UWS) both during the isolation of islets (using the Liberase enzyme blend) and purification of the islets using our novel Iodixanol-UWS density gradient.

Xeno transplantation of these 1-day-cultured pig islets restored normal blood sugar levels in diabetic mice.

PDF slideshow oral presentation Michel van der Burg, Cell Transplant Society congress 1999 in Montreux, Switzerland

Iodixanol-UWS Purification and Culture of Pig Islets Xeno Transplants • Cell Transplant Society 1999 • Michel van der Burg • Miracles.Media • @1MEMO 20250202_2 • TakeNode 8bd79256-78b2-4d8e-8d48-6da41102dc2d • Download file available below 1MEMO_20250202_2

Notes

1) Van der Burg MPM, Rijkelijkhuizen JKRA, Zwaan RP, Bouwman E. Adult pig islet recovery during Liberase isolation, OptiPrep purification and culture for transplantation in nude mice. 4th International congress of the Cell Transplant Society, Montreux (Switzerland) March 21–24, 1999 .

2) Van der Burg MPM, Rijkelijkhuizen JKRA, Zwaan RP, Bouwman E. Adult pig islet recovery during Liberase isolation, OptiPrep purification and culture for transplantation in nude mice (Abstract). Cell Transplant 1999; 8: 185. Download abstract, available below 1MEMO_20250202_3

Citation info : Iodixanol-UWS Purification and Culture of Pig Islets Xeno Transplants • Cell Transplant Society 1999 • Michel van der Burg • Miracles.Media • @1MEMO 20250202 • TakeNode f9d1fdc5-21e4-4932-b995-4c97639945fe • URL michelvanderburg.com/2025/02/02/

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) , and 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.

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.

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 .

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 Islets Transplant Team • Michel van der Burg • Miracles.Media • @1MEMO 20250125 • URL michelvanderburg.com/2025/01/25/

Entero Insular Axis • @1MEMO 20250123

Gastro-Entero-Pancreatic-System • Michel van der Burg • Miracles.Media • @1MEMO 20250123_1 • TakeNode 5b4fa0c5-cecb-45ba-aa39-6df4c833ed43

My first slide in the January 1988 Workshop of the Dutch Diabetes Research Society* in Oosterbeek, Holland, on our new Pancreas & Islet Transplantation Program that had just started in 1988, introduced this still undeveloped field of research the Gastro-Entero-Pancreatic-System (1).

This system ( GEPS ) in which the gastro-intestinal hormones influence the secretion of insulin and other hormones from the pancreatic islets – the “entero-insular” axis – is changed in transplantation of the pancreas or isolated islets of Langerhans.

Insulin feedback on the gut hormone CCK • Michel van der Burg • Miracles.Media • @1MEMO 20250123_2 • TakeNode ac392976-fa14-4d1e-95bb-84e5808ee443

Evidence of insulin feedback on the gut hormone CCK was presented with this poster the next year at the Holland Digestive Disease Week congress in the RAI in Amsterdam (2).

Notes

1) Workshop of the Dutch Diabetes Research Society*, Oosterbeek (The Netherlands) January 22–23, 1988.

2) Van der Burg MPM, Guicherit OR, Gooszen HG, Jansen JBMJ, Frölich M, Lamers CBHW. Evidence for insulin-feedback on fasting CCK in dogs. Holland Digestive Disease Week, Amsterdam (The Netherlands) June 21–24, 1989.

* NVDO – now known as : Dutch Association for Diabetes Research – https://www.nvdo.online/en/homepage-english/
Award – The year before I received the Dutch Diabetes Research Society 1987 Master’s
thesis award for my master’s thesis “Effect of cyclosporine-A on the endocrine pancreas”
(received at the Spring meeting of the Dutch Diabetes Research Society, Utrecht, The Netherlands, April 4, 1987).

Update 20250124 – added NVDO details and 1987 award master’s thesis “Effect of cyclosporine-A on the endocrine pancreas”

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

Transplants of UW-Isolated Islets • Transplantation Society 1990 Paper • @1MEMO 20250118

Congress of The Transplantation Society, Lobby of the Fairmont Hotel, San Francisco, California, USA, August 1990 • Michel van der Burg • Miracles.Media • @1MEMO 20250118_1 • TakeNode 4af71bca-edaa-4adb-9dce-556534844f5b


Following papers presented in 1989 demonstrating that over 90% pure islets are isolated from pancreases when using the UW organ preservation solution (1), the outcome of transplantation of highly purified UW-isolated islets was reported in a proceedings paper presented August 1990 at the XIII International Congress of The Transplantation Society in San Francisco, USA (2,3).
The Transplantation Proceedings paper, published Feb 1991 is now available online below (3).

Notes

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

2) Van der Burg MPM, Guicherit OR, Ploeg RJ, Frölich M, Bruijn JA, Scherft JP, Gooszen HG.
Metabolic control after autotransplantation of highly purified canine pancreatic islets isolated in UW-solution. XIII International Congress of The Transplantation Society, San Francisco (USA) August 19–24, 1990.

3) van der Burg MPM, Guicherit OR, Ploeg RJ, Frölich M, Bruijn JA, Scherft JP, Gooszen HG. Metabolic control after autotransplantation of highly purified canine pancreatic islets isolated in UW solution. Transplant Proc. 1991 Feb;23(1 Pt 1):785-6. PMID: 1990691. PDF available below

Citation info : Transplants of UW-Isolated Islets • Transplantation Society 1990 Paper • Michel van der Burg • Miracles.Media • @1MEMO 20250118 • URL michelvanderburg.com/2025/01/18/

Pancreatic Islets UWS Series 1989 • Kodak PhotoCD • @1MEMO 20250103

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).

Notes

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) 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/