Assessment of isolated islet equivalents • Cell Transplant Society 1996 • @1MEMO 20251205

Assessment of isolated islet equivalents • Cell Transplant Society 1996 • Michel van der Burg • Miracles.Media • 1MEMO_20251205_1 • Poster 3rd International Congress Cell Transplant Society, Miami (USA) Sep 29 – Oct 2, 1996 • TakeNode 1300e7cd-85a4-4cd0-9cbc-a88746e625ab • #IEQ #diabetes #islets #transplant #methods #CTRMS

IEQ – Islet Equivalent

IEQ islet stands for Islet Equivalent, a standard unit used to measure the total volume of islets (clusters of insulin cells and other hormone-producing cells in the pancreas). It is defined as a single spherical islet with a diameter of 150 µm. The IEQ is a crucial parameter for assessing the quantity of islets for procedures like clinical islet transplantation, which is a treatment for type 1 diabetes.

Modified international procedure

Following a consensus report in 1989 – 1990 by Ricordi et al (1a, 1b) on islet isolation assessment, the total volume of isolated islets is generally expressed in the number of islet equivalents (IEQs) — defined as islets of 150 µm diameter— and many centers use the advocated now classic international procedure (CIP) of sizing all islets in classes with 50-µm increments (i.e., 50–100, 100–150, etc.) for calculation of the number of IEQs. For each class the number of IEQs are calculated by multiplying the islet counts with a conversion factor — based on the mean volume of that class.

A modified international procedure — based on our conventional Leiden procedure (2,3) with islet sizing in classes with 25-µm increments — is suggested for accurate assessment of the IEQs especially when isolation yields mostly smaller islets, in our paper ‘Assessment of isolated islet equivalents’ presented at the 3rd International Congress Cell Transplant Society, Miami (USA) Sep 29 – Oct 2, 1996, in both a poster (4) , and proceedings paper (5). A photo of the original poster , (retrieved somewhat wrinkled 30 years later from my archive), is posted here, as well as a pdf from the (corrected proof) manuscript of the proceedings paper below (6).

The Cell Transplant Society was founded in 1991, and has been renamed the Cell Transplant and Regenerative Medicine Society (CTRMS).

Notes

1a. 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.

1b. Quantitative And Qualitative Standards For Islet Isolation Assessment In Man And Large Mammals. International Workshop during the 2nd Congress on Pancreas and Islet Transplantation (1989). Camillo Ricordi. Archive Michel van der Burg • Miracles•Media • 1MEMO_20251206_07 . Available from Dec 6, 2025 URL https://michelvanderburg.com/2025/12/06/

2. Van der Burg MPM, Guicherit OR, Frölich M, Scherft JP, Prins FA, Bruijn JA, Gooszen HG. Assessment of islet isolation efficacy in dogs. Cell Transplant. 1994 Jan-Feb;3(1):91-101. doi: 10.1177/096368979400300113. PMID: 8162296.

3. Paper (Notes 2) included as Chapter 3 in my doctoral thesis (Leiden University, November 1994) : Assessment of islet isolation efficacy in dogs. In : Van der Burg MPM. Pancreatic islet transplantation: studies on the technique and efficacy of islet isolation and transplantation ( Chapter 3). (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 3 , URL https://scholarlypublications.universiteitleiden.nl/access/item%3A3486610/view

4. Van der Burg MPM, Scheringa M, Basir I, Bouwman E. Assessment of isolated islet equivalents. Poster presented at the Third Int. Congress Cell Transplant Soc., Miami (USA) Sept. 29 – Oct. 2, 1996.
In : Assessment of isolated islet equivalents • Cell Transplant Society 1996 • Michel van der Burg • Miracles.Media • @1MEMO 20251205 • URL https://michelvanderburg.com/2025/12/05 • File 1MEMO_20251205_1 • TakeNode 1300e7cd-85a4-4cd0-9cbc-a88746e625ab

5. Van der Burg MPM, Scheringa M, Basir I, Bouwman E. Assessment of isolated islet equivalents. Transplant Proc. 1997 Jun;29(4):1971-1973. doi: 10.1016/s0041-1345(97)00188-7. PMID: 9193483.

6. Manuscript (corrected proof for Transplant Proc paper PMID: 9193483). Van der Burg MPM, Scheringa M, Basir I, Bouwman E. Assessment of isolated islet equivalents • 1MEMO_20251205_2 • TakeNode 48380f3c-b3f7-416e-90bb-ad6c53129e46 • PDF available below , File 1MEMO_20251205_2

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#IEQ #diabetes #islets #transplant #methods #CTRMS

Citation info : Assessment of isolated islet equivalents • Cell Transplant Society 1996 • Michel van der Burg • Miracles.Media • @1MEMO 20251205 • TakeNode 1300e7cd-85a4-4cd0-9cbc-a88746e625ab / 48380f3c-b3f7-416e-90bb-ad6c53129e46 • URL https://michelvanderburg.com/2025/12/05

GLP-1 blood sugar regulation in islet transplants • AIDSPIT 1994 • @1MEMO 20251114

Poster 13th Workshop of the AIDSPIT Study Group , Igls (Austria) January 23–25, 1994• Digitally remastered by author, publisher, M.P.M. van der Burg • Miracles•Media • 20251114 • TakeNode 810cc881-d084-4d2e-b252-d432918b1946 • #GLP1

GLP-1 blood sugar regulation in islet transplants

GLP-1 (glucagon-like peptide-1) is now well-known from the anti-diabetic drugs that mimic the action of this natural hormone GLP-1, to treat type 2 diabetes and obesity. They work by stimulating insulin release, reducing glucagon secretion, slowing stomach emptying, and suppressing appetite, which leads to lower blood sugar and weight loss.

May 1992 we were the first to show direct potentiation of the insulin response from isolated islets by a (near-)physiological dose of the gut hormone GLP-1 during perifusion (in vitro) of canine islets at 7.5-10 mM glucose levels (1,2).

Jan 1994 we next showed this incretin effect of GLP-1 also after islet transplantation (in vivo, in dogs) in this poster (3) and abstract (4) presented at the 13th Workshop of the AIDSPIT (aka AIDPIT) Study Group , Igls, Austria, January 23–25, 1994.

Background of the work was posted earlier this year (5) and the work was published Nov 1994 in my PhD thesis Pancreatic islet transplantation , available online (6).

Notes

1) Van der Burg MPM, Guicherit OR, Scherft JP, Frölich M, Terpstra JL, Gooszen HG. Function after intrasplenic transplantation of islets of Langerhans in dogs (translated from dutch: Functie na intralienale transplantatie van eilandjes van Langerhans in de hond). 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 •

4) Metabolic control after canine islet transplantation. Van der Burg M.P.M., Guicherit O.R., van Suylichem P.T.R., Frölich M., van Deijnen J.H.M. , Gooszen H.G. (Leiden, The Netherlands; Groningen, The Netherlands). Horm metab Res 1994; 26: 63. (Abstract). View/Download file 1MEMO_20251113_2

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5) 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/

6) 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

PM – Recording of the 13th AIDSPIT seminar on lessons from clinical islet transplantation was posted yesterday (7).

7) Clinical Islet Transplantation 13th AIDSPIT • @1MEMO 20251113 • URL https://michelvanderburg.com/2025/11/13/clinical-islet-transplantation-13th-aidspit-1memo-20251113/

#GLP1 #diabetes #islets #transplant #AIDSPIT

Updates

20251127 title updated – insert : AIDSPIT 1994

Citation info : 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

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🔗
https://michelvanderburg.com/wp-content/uploads/2025/02/1memo_20250202_3.pdf

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/

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

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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/

Purification Islets in Iodixanol-UWS • Leiden Start 1996 • @1MEMO 20250126

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/

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

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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/