August 1995, I started designing the clinical promising islet purification solution of Iodixanal in UW-Solution (UWS). I mixed Optiprep – a 60 % solution of iodixanol in water – with a 2-times concentrated UWS, to prepare this density gradient solution. The first standard operation procedure of this Iodixanol-UWS gradient for our pig islet isolation research was completed November 1995.
This purification solution was a logical follow-up of our highly succesful Percoll-UWS density gradient — a similar solution of impermeants (that do not readily enter cells) with similar osmolarity (close to that of the tissue) , more practical though, and with the important advantage that iodixanol is clinical tested.
The Leiden Islet Lab had just moved into the Surgery Lab in the new LUMC building, and the islet team had grown, focussing on xenotransplantation. With more people isolating pig islets, more convenient solutions were tried.
Both Percoll-UWS and Histopaque-UWS were being used from 1992 for small scale islet isolations from juvenile pig pancreases.
July 1996, I introduced the Optiprep-UWS gradient to replace our Percoll-UWS gradient for larger scale porcine islet isolations.
The work was first presented September 1997, both in a poster presented at the Xenotransplantation Congress in Nantes , France (1), and later that month in two talks at the 6th Congress of the International Pancreas and Islet Transplant Association (IPITA) in Milan (Italy). The slideshow of the first talk (2) will be online at this site soon. Here the remastered slideshow of the 2nd talk at the 6th IPITA Congress in Milan, presented Saturday, 27th September, 1997 (3).
Notes
1) Van der Burg MPM, Basir I, Bouwman E. Non-traumatic porcine islet density gradient purification in a novel iodixanol in University of Wisconsin solution. The 4th Int. Congress for Xenotransplantation, Nantes (France) Sept. 7–11, 1997. Online in : Purification Islets in Iodixanol-UWS • Leiden Start 1996 • Michel van der Burg • Miracles.Media • @1MEMO 20250126 • URL michelvanderburg.com/2025/01/26/
2) Van der Burg MPM, Basir I, Bouwman E. No porcine islet loss during density gradient purification in a novel iodixanol in University of Wisconsin solution. Sixth Congress of the Int. Pancreas and Islet Transplant Association (IPITA), Milan (Italy) Sept. 24–27, 1997.
3) Van der Burg MPM, Basir I, Zwaan RP, Bouwman E. Porcine islet preservation during isolation in University of Wisconsin solution. Sixth Congress of the Int. Pancreas and Islet Transplant Association (IPITA), Milan (Italy) Sept. 24–27, 1997.
Milan Papers • @1MEMO 20250205 • Manuscripts (Preprints) and Abstracts copies of the presentations at the IPITA 1997 meeting in Milan (Italy). PDF downloads at michelvanderburg•com/2025/02/05/
Updates
Update 20250128 – update intro design timeline
Update 20250205 – added link to manuscripts and abstracts
Citation info : Porcine Islet Preservation In UWS • IPITA 97 • Michel van der Burg • Miracles.Media • @1MEMO 20250127 • TakeNode 6d6fca2e-014c-40cf-8110-725b267c0b0e • URL michelvanderburg.com/2025/01/27/
Purification Islets in Iodixanol-UWS • Leiden Start 1996 • Michel van der Burg • Miracles.Media • @1MEMO 20250126_1 • TakeNode c2a26daf-2c4f-4051-931d-16babc872c82
August 1995, I started designing the clinical promising islet purification solution of Iodixanal in UW-Solution (UWS). I mixed Optiprep – a 60 % solution of iodixanol in water – with a 2-times concentrated UWS, to prepare this density gradient solution. The first standard operation procedure of this Iodixanol-UWS gradient for our pig islet isolation research was completed November 1995.
This purification solution was a logical follow-up of our highly succesful Percoll-UWS density gradient — a similar solution of impermeants (that do not readily enter cells) with similar osmolarity (close to that of the tissue) , more practical though, and with the important advantage that iodixanol is clinical tested. The Leiden Islet Lab had just moved into the Surgery Lab of the new LUMC building, and the islet team had grown, focussing on xenotransplantation. With more people isolating pig islets, more convenient solutions were tried.
Both Percoll-UWS and and the more convenient Histopaque-UWS were being used from 1992 for small scale islet isolations from juvenile pig pancreases.
July 1996, I introduced the Optiprep-UWS gradient to replace our Percoll-UWS gradient for larger scale porcine islet isolations , in comparison with the Histopaque gradient.
This work was first presented September 1997, both in this poster presented at the Xenotransplantation Congress in Nantes (France) and later that month also in a talk at the 6th Congress of the International Pancreas and Islet Transplant Association (IPITA) in Milan (Italy) — presentations that will be online at this site soon.
Notes
Van der Burg MPM, Basir I, Bouwman E. Non-traumatic porcine islet density gradient purification in a novel iodixanol in University of Wisconsin solution. The 4th Int. Congress for Xenotransplantation, Nantes (France) Sept. 7–11, 1997.
Update 20250128 – update intro design timeline
Citation info : Purification Islets in Iodixanol-UWS • Leiden Start 1996 • Michel van der Burg • Miracles.Media • @1MEMO 20250126 • URL michelvanderburg.com/2025/01/26/
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 shownhere: 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
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.
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/
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/
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/
Montage of 100 years diabetes discoveries in educational wall display (created in 1998) from the Joslin Diabetes Center and Roche Diagnostics.
Music : Someday, Maybe by Maya Belsitzman & Matan Ephrat | Artlist
Citation info : Diabetes Discoveries Display • Michel van der Burg • Miracles.Media • @1MEMO 20250117 • TakeNode 00ff4392-ea87-40fb-90a2-ada2cbb77efb • URL michelvanderburg.com/2025/01/17/
Leiden Islet Isolation Chamber • Michel van der Burg • Miracles.Media • @1MEMO 20250116 • TakeNode 398303fe-928a-4c53-839e-9dde0e7d8ec6
Following a working visit February ’92 studying pig islet isolation at the ‘Fondation Transplantation’ in Strasbourg -Hautepierre, France (1) , I designed this islet isolation chamber March 1992 for use in our Leiden Islet Laboratory , together with Gerard Verschagen , head of the precision mechanics workshop of the Laboratory of Physiology of the University Hospital Leiden (AZL , now LUMC), who manufactured this and other of our islet isolation devices.
The chamber was designed with support for use together with the Retsch Vibro Sieving Machine , purchased earlier for our Leiden Islet Laboratory, a vibrating sieving machine I had used in the 70s for isolation cell nuclei (2). The design was based on the Ricordi chamber published 4 years earlier (3).
The drawing was originally designed and produced on a Macintosh computer March 1992, using the MacDraw II application. That Mac file was remastered today in LibreOffice Vanilla, by straightening most of the lines that are slanted after opening in LibreOffice and correcting the font changes. So , not accurate now probably … just for illustration the history of progress in our Leiden Islet Laboratory, and love for art 😉
Notes
1) Xeno Islets • Michel van der Burg • Miracles.Media • @1MEMO 20250113 • URL michelvanderburg.com/2025/01/13/
2) Mennes AM, Bouman H, Van der Burg MPM, Libbenga KR. RNA synthesis in isolated tobacco callus nuclei, and the influence of phytohormones. Plant Sci Lett 1978; 13: 329– 339, ISSN 0304-4211, https://doi.org/10.1016/0304-4211(78)90210-9.
3) Piemonti L, Pileggi A. 25 Years Of The Ricordi Automated Method For Islet Isolation. CellR4 Repair Replace Regen Reprogram. 2013;1(1):e128. PMID: 30505878; PMCID: PMC6267808. URL https://www.cellr4.org/article/128
Citation info : Leiden Islet Isolation Chamber • Michel van der Burg • Miracles.Media • @1MEMO 20250116 • URL michelvanderburg.com/2025/01/16/
