Tag: research

Primate Islet Isolation and Purification in Iodixanol-UWS • @1MEMO_20260425

Primate Islet Isolation and Purification in Iodixanol-UWS • @1MEMO_20260425

by Michel van der Burg , April 25th, 2026

Synopsis

In early 1999, a pilot study at the Biomedical Primate Research Centre in Holland successfully tested an innovative Iodixanol-UWS density gradient solution for isolating and purifying islets from four macaques, achieving 94% purity and 90% recovery. Viability of the purified islets was confirmed at 98% after one day in culture. The strict biosafety protocols required for this primate work provided valuable preparation for the subsequent launch of human islet isolations at Leiden University Medical Center. The protocol was further validated in a second series of eight rhesus islet isolations in 2000.

February 1999

In early February 1999, a few weeks before we received the green light for the official launch of the clinical islet transplantation project (1) in our Leiden University Medical Center (LUMC), I also started preparations to isolate non-human primate islets at the Biomedical Primate Research Centre in Holland.

At the time, we were already collaborating with researchers from the Biomedical Primate Research Centre for xenotransplantation of purified pig islets in macaque monkeys (2).

With our innovative purification solution — made from Iodixanol (the radio contrast agent Optiprep/Visipaque) , mixed with University of Wisconsin solution (UWS), the solution traditionally used for cold storage of human donor organs — we had successfully isolated and purified the islets of Langerhans from pig pancreases since 1996, and transplanted them into mice, rats, and cynomolgus macaque monkeys (2, 3, 4).

This Iodixanol-UWS purification solution had been successfully trialed on human donor islets during my 1998 visit to the Diabetes Research Institute (DRI) in Miami (5,6).

I had now been asked at our Surgery department (LUMC, Leiden, Holland) to examine whether this isolation method using Iodixanol-UWS can be used also in the non-human primate model , with a view to the application for a new research project on allo-transplantation of islets in Rhesus macaques, and in vitro research into the immunogenicity of these purified islets.

For these pilot experiments, the islets were isolated from donor pancreases procured by Michel van der Burg (me), and the transplant surgeons André Baranski, Jan Ringers, and Jan IJzermans, from one cynomolgus (Macaca fascicularis) and three rhesus macaques (Macaca mulatta), that were obtained during surgery upon euthanasia of these laboratory animals for the termination of unrelated experiments by other research groups at the Biomedical Primate Research Centre.

I had previously watched rhesus islet isolation at the DRI in Miami during that working visit in 1998. So , now before starting the isolations the first week of March 1999, I contacted the experienced DRI researcher Norma Kenyon for advise on the optimal donor age , and optimal amount of enzyme (Liberase-HI) for digestion of the pancreas in this species.

Following digestion of the pancreas with the Liberase-HI enzyme in Hanks’ balanced salt solution , the islets were isolated with our manual method in cold UWS (ViaSpan), and purified by centrifugation in the cold Iodixanol-UWS density gradient solution.

Excellent results were obtained in this pilot of 4 primate islet isolations .
Before the purification step , after digestion of the pancreas , the yield of isolated islets amounted to a mean 3697 islets / gram pancreas (IEQ; islet equivalents*).

After purification of these islets in our Iodixanol-UWS density gradient solution , virtually pure islets were obtained (a mean 94% purity) , with virtually no loss of islets (a mean 90 % recovery).

The purified islets were stored in suspension in culture medium up to 1 week after isolation. Both before culture and after 4 days culture, aliquots of the rhesus islets were prepared for analysis of the immunogenicity of the islets in a Mixed Lymphocyte Islet Culture (MLIC) by co-worker Krista Haanstra.

I photographed the isolated cynomolgus islets both before culture (stained red with dithizone), and after one day culture (not stained, in the petri dishes used for culture).


Cynomolgus monkey islets purified in Iodixanol-UWS • 1MEMO_20260425_1 • Michel van der Burg • Miracles•Media • TakeNode 893e099a-13b2-42cd-a3e9-17bcbe14d3d9 • Islets not cultured, identified by staining red with dithizone, after overnight preservation in cold UWS (due to logistics).


Cynomolgus monkey islets purified in Iodixanol-UWS • 1MEMO_20260425_2 • Michel van der Burg • Miracles•Media • TakeNode 606380dc-ae91-461e-ab6c-2c24186676de • Islets cultured one day at 37°C, not stained.

Survival of 98% of the islets after staying one day in suspension in a culture solution at 37°C demonstrated the excellent viability of these cynomolgus islets.
The viability was confirmed by staining these cultured islets with a mixture of two fluorescent dyes — acridine orange and propidium iodide (AO/PI). Fluorescence microscopy shows the live (green) cells , and few dead (red/yellow) cells in these islets.


Cynomolgus monkey islets purified in Iodixanol-UWS • 1MEMO_20260425_3 • Michel van der Burg • Miracles•Media • TakeNode 7666a0a1-7876-4c85-9bd6-30b4ae780028 • Islets cultured one day at 37°C. Fluorescence microscopy shows the live (green) and few dead (red/yellow) cells in these islets. Staining with a mixture of two fluorescent dyes —acridine orange and propidium iodide (AO/PI).

The strict biosafety and biosecurity precautions required for this work, especially due to the risk of infection via aerosols during trituration, sieving, and pouring of the large volumes of tissue and cell suspensions from these non-human primates, proved valuable preparation for the subsequent launch, later that month—March 1999—of human islet isolations from donor organs, in our provisional human islet laboratory at the Department of Surgery—pending the completion of the LUMC GMP facility with a cleanroom for our clinical islet laboratory, that I was preparing together with Amon Wafelman the executive head of the future GMP Facility.

I continued this project of rhesus islet isolation, purification and banking, with in vitro research into the immunogenicity of these purified islets, a year later (July-Dec 2000), coaching medical student Gabe Bleeker who corroborated the efficacy of our protocol in that second series of eight rhesus islet isolations (7). He would also assist me at the time in our islet laboratory with the automated ‘Ricordi’ method for human islet isolation, islet banking and quality control by transplants of aliquots of the human islets in nude mice.

Notes

* IEQ : One islet equivalent (IEQ), is defined as the volume of one islet with a 0.15 mm diameter. Because there a more smaller than large islets in the pancreas , the volume of islets is used to indicate islet yield, and expressedin number of ‘islet equivalents’.

1. Ekkelboom J. Hulp voor suikerzieke klieren. In: Volkskrant April 10th 1999 https://www.volkskrant.nl/wetenschap/hulp-voor-suikerzieke-klieren~b7046616

2) Successful Islet Transplantation After Purification in Iodixanol-UWS • IPITA 1999 Sydney • @1MEMO 20260326 • Michel van der Burg • Miracles.Media • URL michelvanderburg.com/2026/03/26/

3) Innovative Islet Purification in Iodixanol-UWS • IPITA 97 • Michel van der Burg • Miracles.Media • @1MEMO 20250128 • URL michelvanderburg.com/2025/01/28/

4) Iodixanol-UWS Purification for Porcine Islet Transplantation • AIDSPIT 1998 • Michel van der Burg • Miracles.Media • @1MEMO 20250131 • TakeNode 1f185515-7aeb-44ac-b721-2cec76df67b7 • URL michelvanderburg.com/2025/01/31/

5) Human Islet Isolation • DRI Miami 1998 • Michel van der Burg • Miracles.Media • @1MEMO 20250204 • TakeNode 86e4a319-a769-44d5-8fa5-de2ca90ab63c • URL michelvanderburg.com/2025/02/04/

6) Efficacy of the novel iodixanol-UWS density gradient for human islet purification • Igls Aidspit 1999 • Michel van der Burg • Miracles.Media • 20241202 • URL michelvanderburg.com/2024/12/02/

7) Protocol for the isolation of islets of Langerhans from the pancreas of the rhesus monkey (dutch : Protocol voor isolatie van eilandjes van Langerhans uit het pancreas van de rhesus-aap) • Studies on the isolation and immunogenicity/immunology of monkey (rhesus) islets • Gabe B. Bleeker (MSc student Medicine) at the Department of Surgery of the Leiden University and the BPRC – TNO centre.


Cover Bleeker Report Rhesus Islet Isolation • 1MEMO_20260425_4 • Michel van der Burg • Miracles•Media • TakeNode 96bd9197-71a5-4c19-9540-264b1ba74be4 • Protocol for the isolation of islets of Langerhans from the pancreas of the rhesus monkey. Cover research report, MSc student Medicine, Gabe Bleeker (Dec 2000).

#islets #islet #Langerhans #isolation #purification #culture #isletbank #QC #immunogenicity #GMP #facility #LUMC #Holland #Netherlands #Leiden #hospital #primate #human #monkey #rhesus #cynomolgus #macaque #donor #surgery #clinical #laboratory #optiprep #iodixanol #ViaSpan #density #gradient #UWS #pancreas #MLIC #UW #university #Wisconsin #transplantation #xeno #mouse #diabetes #man #history #research #1memo #michelvanderburg #Bleeker #Ricordi #DRI #Miami

Citation info : Primate Islet Isolation and Purification in Iodixanol-UWS • @1MEMO_20260425 • Michel van der Burg • Miracles.Media • URL michelvanderburg.com/2026/04/25/

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_04Download

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

1MEMO_20251206_07Download

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

1MEMO_20251206_04Download

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

1MEMO_20251206_05Download

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

Glycemic control mechanisms after canine islet autografting • IPITA 1995• @1MEMO 20251204

Glycemic control mechanisms after canine islet autografting • IPITA 1995 • Michel van der Burg • Miracles.Media • @1MEMO 20251204_1 • Talk, Tuesday June 20, 1995 at 10:30, 5th IPITA, Eden Roc Resort Hotel, Miami Beach, FL (USA) • Digitally remastered by author, publisher, Michel van der Burg • TakeNode 5227c200-e029-4406-b344-15350fe3b93d • #GLP1 #GIP #diabetes #islets #transplant

Pioneer work on GLP-1 and GIP incretin hormones

Slideshow (digitally remastered) of my talk Tuesday June 20, 1995 at 10:30, at the 5th International Congress on Pancreas and Islet Transplantation (IPITA), in Miami Beach, FL (USA). My first talk at a world congress presenting the outcome of all our detailed metabolic studies in our preclinical model of canine islet autotransplantation , including our pioneer work on the incretin effects of the gut hormones GLP-1 (glucagon-like peptide-1) and GIP (Glucose-dependent Insulinotropic Polypeptide) — now, in 2025, well-known from the drugs that mimic the action of these natural hormones, to treat type 2 diabetes and obesity, by stimulating insulin release, improving blood sugar control, and reducing appetite.

May 1992 we were the first to show direct potentiation of the insulin response from isolated islets by (near-)physiological doses of both the gut hormones GLP-1 and GIP during perifusion (in vitro) of canine islets at 7.5-10 mM glucose levels (1,2), and January 1994 we next confirmed the incretin effect of a (near-)physiological dose of GLP-1 after canine islet transplantation , in a poster presented at the 13th Workshop of the AIDSPIT (aka AIDPIT) Study Group , Igls, Austria, January 23–25, 1994 (3).

Background of the work was posted earlier this year (4) and the work was published Nov 1994 in my PhD thesis Pancreatic islet transplantation , available online (5).


Welcome Reception 5th IPITA on Sunday 18 June 1995, at the congress venue , the Eden Roc Resort Hotel, in Miami Beach, FL (USA) • Michel van der Burg • Miracles.Media • @1MEMO 20251204_2 • TakeNode 8eb04df1-8280-4de3-a206-4b63413c3025

June 1995, 5th IPITA Talk

Tuesday June 20, 1995 at 10:30, at the 5th International Congress on Pancreas and Islet Transplantation (IPITA), in Miami Beach, FL (USA), was my first talk at a world congress presenting the outcome of all our detailed metabolic studies in the canine islet transplants , including the incretin effect of GLP-1, and also our findings with isolated canine islets during perifusion, in vitro, of the direct insulinotropic effects of the gut hormones GIP and GLP-1 (6) . That slideshow presentation (digitally remastered*) is posted here (1MEMO 20251204_1).

The proceedings paper delivered at the 5th IPITA is included in the Notes (7) , as well as the referenced previous papers (8,9)

Notes

1. 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 • URL https://michelvanderburg.com/2024/09/10/gut-factors-controlling-pancreatic-islets-20240910/

2. 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.

3. Metabolic control after canine islet transplantation. M.P.M. van der Burg, P.T.R. van Suylichem, O.R. Guicherit, J.H.M. van Deijnen, M. Frölich, and H.G. Gooszen (Universities of Leiden & Groningen, The Netherlands). Poster presented at the 13th Workshop of the AIDSPIT Study Group , Igls, Austria, January 23–25, 1994 • In : GLP-1 blood sugar regulation in islet transplants • AIDSPIT 1994 • Michel van der Burg • Miracles.Media • @1MEMO 20251114 • TakeNode 810cc881-d084-4d2e-b252-d432918b1946 • URL https://michelvanderburg.com/2025/11/14

4. Background of this work was posted in Dutch Islets Transplant Team • @1MEMO 20250125 • URL https://michelvanderburg.com/2025/01/25/dutch-islets-transplant-team-1memo-20250125/

5. Van der Burg MPM. Pancreatic islet transplantation: studies on the technique and efficacy of islet isolation and transplantation. (Doctoral Thesis, Leiden University, 1994), Paperback (1994, Nov 9) Boskoop: Van der Burg (ISBN 9080216410); E-book (2022, Oct 25) Boskoop: Michel van der Burg | Miracles•Media ( ISBN 9789080216402). Retrieved (Dec 4th, 2025) from Leiden University Scholarly Publications, Persistent URL https://hdl.handle.net/1887/3486604 .

6. Oral presentation : 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 20, 1995.

7. 5th IPITA Proceedings publication : 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. PDF available below PMID_8539903

PMID_8539903Download

Referenced previous publications :


8. Van der Burg MPM, Gooszen HG. The metabolic efficiency of islet grafts: an overview. In: Islet transplantation — current status of clinical application and experimental results. Hesse UJ , Pichlmaier H, Eds., Lengerich Germany, Wolfgang Pabst Verlag, 1992, p.93–99. Pabst hash code 0383b3abad3ae774b146ea0425c2227a PDF available below 1MEMO_20251204_4

1MEMO_20251204_4Download

9. Van der Burg MPM, Guicherit OR, Scherft JP, Lemkes HHPJ, Frölich M, Gooszen HG. Postprandial performance after canine islet transplantation: the importance of gut factors (Abstract). Neth J Med 1992; 41: A25. PDF available below 1MEMO_20251204_3

1MEMO_20251204_3Download
Other previous publications :

10. Van der Burg MPM, Guicherit OR, Van Suylichem PTR, Frölich M, Van Deijnen JHM, Gooszen HG. Importance of the entero-insular axis for islet graft function (Abstract). Cell Transplant 1994; 3: 257. Abstract – Second International Congress of the Cell Transplant Society May 1–4, 1994 Hyatt Regency Hotel • Minneapolis, Minnesota . https://doi.org/10.1177/096368979400300302 (Abstracts published , posters not presented). PDF available below 10.1177_096368979400300302

10.1177_096368979400300302Download

11. Chapter 8, Doctoral Thesis, Leiden University, November 1994 : Metabolic control after intrasplenic islet autotransplantation in dogs: ß-cell secretory capacity, insulin action, and the enteroinsular axis. Michael P.M. van der Burg, Paul T.R. van Suylichem, Onna R. Guicherit, Marijke Frölich, Herman H.P.J. Lemkes, and Hein G. Gooszen. In : Van der Burg MPM. Pancreatic islet transplantation: studies on the technique and efficacy of islet isolation and transplantation ( Chapter 8). (Doctoral Thesis, Leiden University, 1994), Paperback (1994, Nov 9) Boskoop: Van der Burg (ISBN 9080216410); E-book (2022, Oct 25) Boskoop: Michel van der Burg | Miracles•Media ( ISBN 9789080216402). Retrieved (Nov 24th, 2025) from Leiden University Scholarly Publications, Persistent URL https://hdl.handle.net/1887/3486604 .
Direct link to file Chapter 8 , URL https://scholarlypublications.universiteitleiden.nl/access/item%3A3486615/view .

12. Doctoral Thesis, Leiden University, November 1994 (Chapter 6) : lnsulinotropic properties of cholecystokinin, gastric inhibitory polypeptide, and glucagon-like peptide-1 during perifusion of short-term cultured canine isolated islets. Michael P.M. van der Burg, Onna R. Guicherit, Marijke Frölich and Hein G. Gooszen. In : Van der Burg MPM. Pancreatic islet transplantation: studies on the technique and efficacy of islet isolation and transplantation ( Chapter 6). (Doctoral Thesis, Leiden University, 1994), Paperback (1994, Nov 9) Boskoop: Van der Burg (ISBN 9080216410); E-book (2022, Oct 25) Boskoop: Michel van der Burg | Miracles•Media ( ISBN 9789080216402). Retrieved (Nov 24th, 2025) from Leiden University Scholarly Publications, Persistent URL https://hdl.handle.net/1887/3486604 .
Direct link to file Chapter 6 , URL https://scholarlypublications.universiteitleiden.nl/access/item%3A3486613/view

Full papers

13. 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.

14. 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. PDF link https://pure.rug.nl/ws/portalfiles/portal/58359942/096368979700600509.pdf

* 1MEMO 20251204_1 . Digitally remastered presentation, using the images from the original slides handout, and the handout of the text spoken during the original presentation , now read using my personal synthesized voice.

#GLP1 #GIP #diabetes #islets #transplant

Citation info : Glycemic control mechanisms after canine islet autografting • IPITA 1995 • Michel van der Burg • Miracles.Media • @1MEMO 20251204 • URL https://michelvanderburg.com/2025/12/04

Discoveries Deportation Westerbork Film • 20250224

Discoveries Deportation Westerbork Film • 20250224 • The boy, the man, and the woman selected in this edited still of the linked video clip (15 s) URL https://youtube.com/clip/UgkxBw3eso6Bi3vIaR25h_bDWRHSx5EfMylN

Utrecht family identification , almost complete…

Almost certainly, three Jewish people have been recognized in the unique Westerbork film from 1944 (1). This time it concerns the 9-year-old boy Israël Wijnschenk, his father Max Wijnschenk, and his grandmother Betje Kokernoot-van Furth, who all lived in Utrecht (Holland).

Last week, the Dutch public broadcaster NOS (2) reported the news from the Utrecht (Dutch) news site Nieuws030 (3) that it is very likely that three people were recognized again in this film made by the Jewish prisoner and filmmaker Rudolf Breslauer showing the deportation of Jews, Roma and Sinti by train in Camp Westerbork on May 19, 1944.

Image researcher Koen Hulsbos — who previously identified an Amsterdam couple in this deportation train (4) — thought he recognized the young Israël Wijnschenk, a pupil at the time of the Joodse (Jewish) School Utrecht, and presented this to Victor Frederik, researcher of the Joodse School (5,6). The boy, the man, and the woman seem to belong together, and were recognized from family photos, also by family members.

It is certain that Max and his wife Chel (not in the images) returned to Utrecht after the war, their children Israël and his sister Kitty were murdered. Grandma Betje was also gassed in Auschwitz.

A portrait of Israël Wijnschenk is shown at the site of Joods Monument (7).

According to the transport list, there were two other children in that wagon, Joseph Beugeltas (11 years old) and Manfred Studzinsky (7 years old). Joseph Beugeltas appeared to have blond hair, and could not have been it (6). To be completely sure, the researchers are still looking for a photo of Manfred Studzinsky, for comparison…

Notes

1) Deportation Westerbork Film • Edition 2021 | 20210719 | Settela•Com | ISSN 2949-9313 | Footage filmed by Rudolf Breslauer in 1944, courtesy of NIOD | Sound and Vision . URL https://settela.com/2021/07/19/deportation-westerbork-film-20210719/

2) Utrechters ‘vrijwel zeker’ herkend op Westerborkfilm uit 1944. NOS Nieuws Feb 22, 2025. URL https://nos.nl/l/2556858

3) Nieuwe herkenningen in Westerborkfilm ‘bijna zeker’. Jim Terlingen | Nieuws030 . URL https://www.nieuws030.nl/hist030rie/drie-nieuwe-herkenningen-in-westerborkfilm-zo-goed-als-zeker/

4) Amsterdam couple found in Westerbork film • 20241223 | Settela•Com | ISSN 2949-9313 | URL https://settela.com/2024/12/23

5) Joodse school Utrecht. Website. URL https://joodseschoolutrecht.nl

6) Israël op Westerborkfilm? Victor Frederik- Web site Joodse school Utrecht. (Accessed 20250224). URL https://joodseschoolutrecht.nl/nl/Verhalen-over-leerlingen/Kitty-en-Israel-Wijnschenk/Israel-op-Westerborkfilm/

7) Portrait of Israël Wijnschenk. Site Joods Monument. URL https://www.joodsmonument.nl/nl/page/122045/israël-wijnschenk

Citation info : Discoveries Deportation Westerbork Film • 20250224 | Settela•Com | ISSN 2949-9313 | URL https://settela.com/2025/02/24/

Milan Papers • @1MEMO 20250205

Manuscripts (Preprints) and Abstracts copies of the presentations at the IPITA 1997 meeting in Milan (Italy).

1) Van der Burg MPM, Basir I, Zwaan RP, Bouwman E. Porcine islet preservation during isolation in University of Wisconsin solution. Transplant Proc. 1998 Mar;30(2):360-1. doi: 10.1016/s0041-1345(97)01307-9. PMID: 9532079.

PMID_9532079_20250205_1 • Michel van der Burg • Miracles.Media • @1MEMO 20250205_1 • CC BY-NC-ND • TakeNode 406dbe1e-66e3-4edc-acb8-83fdc8ddc5c8

PMID_9532079_20250205_1Download

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. Transplant Proc. 1998 Mar;30(2):362-3. doi: 10.1016/s0041-1345(97)01308-0. PMID: 9532080.

PMID_9532080_20250205_2 • Michel van der Burg • Miracles.Media • @1MEMO 20250205_2 • CC BY-NC-ND • TakeNode c60e0743-946a-4950-b156-7e671593e482

PMID_9532080_20250205_2Download

3) Abstracts

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 (Abstract). Acta Diabetol 1997; 34: 101.

Van der Burg MPM, Basir I, Zwaan RP, Bouwman E. Porcine islet preservation during isolation in University of Wisconsin solution (Abstract). Acta Diabetol 1997; 34: 136.

1MEMO_ 20250205_3 • Michel van der Burg • Miracles.Media • @1MEMO 20250205_3 • CC BY-NC-ND • TakeNode e5b1c598-fc48-4f2a-93ae-526cd4be082e

1MEMO_ 20250205_3Download

Citation info : Milan Papers • Michel van der Burg • Miracles.Media • @1MEMO 20250205 • URL michelvanderburg.com/2025/02/05/

Human Islet Isolation • DRI Miami 1998 • @1MEMO 20250204

Summer 1997, Onno Terpstra, the head of our Surgery Department, asked me to explore our options for starting clinical islet isolation and transplantation in our center – the Leiden University Medical Center (LUMC), and prepare a roadmap.

September 1997, at the IPITA congress in Milan (1) , I learned from Camillo Ricordi, the scientific director of the Diabetes Research Institute (DRI) in Miami – where many guest collaborators work – that visiting the DRI some weeks might be a good option to gain sufficient first work experience in his clinical islet transplantation group.

December 1997, with a ‘Roadmap’, I got the green light to start the operationalization of clinical islet transplantation in the LUMC, first with a working visit to Miami to study the state of the art ‘Ricordi’ method of human islet isolation, and then start the human islet isolation work in our Surgery lab in Leiden.

In 1990 I had already gained some initial research experience in our Leiden Islet Laboratory with a small number of isolations of islets from human donor organs, using our innovative method of density gradient purification based on the UW solution (2).

During the first three months of 1998 I worked intensively with my student colleague Josephine Rijkelijkhuizen so that she would be able to continue our xenotransplantation research project as independently as possible in our Surgery research team.

April 1998, after participating in the 1st Workshop on Clinical Islet Transplantation in New Orleans (3) – the ideal introduction – a fruitful working visit to the DRI in Miami followed (4,5), with intensive collaboration with the DRI team on, among other things, six human islet isolations, and also the simultaneously (parallel) conducted research into the purification of the human islets in our Iodixanol gradient in UW-Solution (6).

Here a slideshow illustrating this team up with the DRI team in Miami , working on human islet isolation and purification in the innovative Iodixanol-UWS gradient, April-May 1998.

Notes

1) Innovative Islet Purification in Iodixanol-UWS • IPITA 97 • Michel van der Burg • Miracles.Media • @1MEMO 20250128 • TakeNode • URL michelvanderburg.com/2025/01/28/

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

3) Invited participant 1st Workshop on Clinical Islet Transplantation, New Orleans (LA, USA) April 17–19, 1998

4) 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)

5) DRI Dream Team • Michel van der Burg • Miracles.Media • @1MEMO 20250105 • URL michelvanderburg.com/2025/01/05/

6) Human Islet Purification Miami 1998 • Michel van der Burg • Miracles.Media • 20181102 • URL michelvanderburg.com/2018/11/02/

Citation info : Human Islet Isolation • DRI Miami 1998 • Michel van der Burg • Miracles.Media • @1MEMO 20250204 • TakeNode 86e4a319-a769-44d5-8fa5-de2ca90ab63c • URL michelvanderburg.com/2025/02/04/

Fresh vs Cultured Pig Islets for Xenografts • NTV Bootcongres 1998 • @1MEMO 20250201

Fresh vs Cultured Pig Islets for Xenografts • NTV Bootcongres 1998 • Michel van der Burg • Miracles.Media • @1MEMO 20250201_1 • TakeNode 71d39e7e-ab5e-42b6-8cf2-a17d464ce132


Van der Burg MPM, Rijkelijkhuizen JKRA, Zwaan RP, Bouwman E. Culture of isolated pig islets pre-xenotransplantation greatly improves the quality and survival of the graft (Kweek van geïsoleerde varkenseilandjes pre-xenotransplantatie verbetert aanzienlijk de kwaliteit en overleving van het transplantaat). Tenth Congress of the Dutch Transplantation Society (Bootcongres 1998), Kerkrade (The Netherlands) April 21–23, 1998.

Download (pdf) NTV bulletin (abstract) & poster , file 1MEMO_20250201

1MEMO_20250201🔗Download

EN – Abstract

PRE-TRANSPLANT SHORT-TERM CULTURE OF ISOLATED PIG ISLETS MARKEDLY IMPROVES THE QUALITY AND SURVIVAL OF THE XENOGRAFT
Van der Burg MPM,* Rijkelijkhuizen JKRA, Zwaan RP, and Bouwman E, Leiden University Medical Centre, Leiden, The Netherlands.

Pre-transplant culture of isolated islets reduces the graft’s immunogenicity in various models. Little is known, however, on the effect of culture in pig islet xenotransplantation — probably, because porcine islets have been found difficult to culture. Because pilot transplants of freshly-isolated pig islets in strongly immunosuppressed rats resulted in primary non function, we first studied 1-7 day culture of the isolated pig islets at 37°C in RPMI plus 10% porcine serum. Islets were isolated from large sows (n =6) by an improved method, resulting in intact islets (size 185±16 µm) and no loss during purification, yielding 2448 islets (IEQs)/g with a >95% purity and 90±2% viability as assessed by acridine orange – propidium iodide (AOPI) staining. During culture, however, islet recovery was 24±9% at day 1 and 17±6% at day 7 (NS vs day 1). In order to delineate whether the culture conditions or the quality of freshly isolated islets caused the islet loss during culture, we compared graft survival in nude mice at 1 mo after transplantation under the kidney capsule of ~2500 fresh islets in normoglycemic recipients or ~1000 cultured islets in STZ-diabetic (>20 mM) recipients. After transplanting fresh islets, histology of the kidneys — sectioned every 500 µm — demonstrated substantial scarring and (near-)absence of islets. Cultured islet transplants, by contrast, rendered 5/6 recipients normoglycemic, and showed a substantial mass of well-preserved islets with little scarring at the grafts’ site. Thus, viability by AOPI-staining of fresh islets poorly predicts the survival in vivo and in vitro. A non-immune mediated disintegration of part of the fresh islets may substantially reduce the functional capacity of the graft, both direct by lowering the effective islet dose, and indirect first because scarring may hamper the engraftment of viable tissue, and second because the cellular debris most probably will attract macrophages and induce the release of harmful cytokines.

Citation info : Fresh vs Cultured Pig Islets for Xenografts • NTV Bootcongres 1998 • Michel van der Burg • Miracles.Media • @1MEMO 20250201 • URL michelvanderburg.com/2025/02/01/