Blurb | Pancreatic islet transplantation | 20221023

Blurb | Pancreatic islet transplantation | 20221023 | Michel van der Burg | Miracles•Media | French flap interior of paperback back cover with illustration of islet isolation and transplantation in the doctoral thesis Pancreatic islet transplantation – ISBN 9789080216402. Studies aiming at transplantation of the pancreatic Islets of Langerhans to prevent, postpone or ameliorate the long-term crippling complications of insulin-dependent diabetes mellitus (IDDM). Paperback published in 1994 ISBN 9789080216419 | 9080216410 , later this month published as eBook (pdf) ISBN 9789080216402.

Illustration of Islet Isolation and Transplantation
(Captions at last page of the dissertation)

1. Paul Langerhans
2. Section of the normal dog pancreas showing islets stained reddish-brown (immunostained for insulin)
3. The author, watching the dog islet isolation procedure in the Minneapolis surgical research laboratory
4. Start of the operation in the dog (From left to right: Professor Hein G. Gooszen, Ms. M. Jane Field (Minneapolis), and Dr. Onno R. Guicherit, at our surgical laboratory)
5. The pancreas is removed
6. Infusion of the collagenase solution via the ducts in the dog pancreas – collagenase leaking from the pancreas is recirculated using a pump (Islet laboratory, at the Department of Cell Biology and Histology, Leiden)
7. During collagenase digestion at 37-39°C the pancreas falls apart (non-stained pancreatic exocrine tissue and free-ed small blood vessel, at low magnification)
8. Dissociated pancreatic tissue
9. Tissue is further dispersed by aspiration in a syringe, and sieved to remove undigested fragments, ducts and vessels ~ demonstrated by Ms. Jane Field at our islet laboratory.
10. Tissue suspension demonstrating low purity of the islets (stained red by dithizone) obtained by dextran gradient separation after isolation in the RPMI tissue culture solution (dark-brown exocrine fragments remain unstained)
11. Pure islet suspension (after dithizone staining) obtained by density separation in Percoll gradients (in University of Wisconsin solution) after islet isolation in the University of Wisconsin solution (islets are only slightly stained due to poor diffusion over the cell membrane in the preservation solution)
12. Section of highly purified islets obtained by dextran density separation after isolation in the University of Wisconsin solution
13. Islets are autotransplanted by infusion in the spleen of the dog
14. Transplanted islet in section of the spleen of one of the dogs shortly after the onset of fasting hyperglycemia at three months posttransplant (immunostained for insulin)
15. Highly purified human islets obtained by Percoll density separation after isolation in the University of Wisconsin solution (immunostained with gold for insulin; not counterstained)

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Reprint | 20221022

Reprint | 20221022 | Michel van der Burg | 1-memo•com | Silent film. Scanning for an ebook reprint – ISBN 9789080216402 – of the doctoral thesis Pancreatic islet transplantation. Studies on the isolation and transplantation of the pancreatic Islets of Langerhans to prevent, postpone or ameliorate the long-term crippling complications of insulin-dependent diabetes mellitus (IDDM). First published as a paperback in 1994 ISBN 9080216410 / 9789080216419 , and later this month published as eBook (pdf). TakeNode ID: 777e40a7-c148-4832-a24a-ff599c1845c5

TAGS #publish #science #donor #pancreas #insulin #therapy #clinical #islets of Langerhans #isolation #transplantation #medicine #biology #diabetes #IDDM #laboratory #research #cure #Leiden University #LUMC #dissertation #PhD #Doctor of Philosophy #publisher #scan #ebook #book #ISBN #9789080216402 #9789080216419 #Holland #Netherlands #TakeNode #1Memo #michelvanderburg

Isolation of Islets of Langerhans for Transplantation in Type-1 Diabetic Patients

Isolation of Islets of Langerhans for Transplantation in Type-1 Diabetic Patients.
Here a film made of my ‘powerpoint’ presentation Feb 22, 2000 – on behalf of our Surgical Department – at the Opening Symposium of the Interdivisional GMP (‘Good Manufacturing Practice’) facility of the Leiden University Medical Centre – the LUMC in Leiden, Holland.

Background
I first started – with a background in biochemistry and philosophy – some 20 years earlier (from 1981) research at the Department of Surgery of the Leiden University Hospital (AZL) in the field of transplantation of the pancreas organ to cure diabetes.

Succesful Experiment Islet Transplantation
From 1986 my focus shifted to innovative procedures for the isolation out of the pancreas organ, of the ca 1 million islets of Langerhans – the insulin producing cell clumps with a size between ca 0.1 to 1 mm , that is 0.004 to 0,04 inch.
In 1989 we performed the first successful autologous transplantations in Holland (in collaboration with the Minneapolis Islet Lab with Jane Field and David Sutherland) – for the first time world-wide with pure islets using our novel procedure of using the organ preservation UW solution (University of Wisconsin / collaboration with dr Robert Carter , Du Pont, UK) during isolation in a pre-clinical large animal diabetes model – with long term transplant functioning with near-normal blood sugar regulation.

First series of human islet isolations , 1989-1990
Next in 1989-1990 we performed a first series of islet isolations from human donor pancreases using our novel techniques of isolation and purification in UW organ preservation solution – in association with a European Concerted Action for the Treatment of Diabetes – the Brussels headed (Daniel Pipeleers) ‘Multicenter program on the treatment of diabetes by islet cell transplantation’.

Exploring human islet work
Subsequently – after some years of exploring options for animal to human islet transplantation , using pig pancreas islets – so-called xenotransplantation – I was asked in 1997 to explore the requirements for operationalization of clinical islet transplantation in the LUMC. December 1997 our Surgical Department decided to go for it.

Establishing the human islet isolation laboratory in Leiden.
In 1998 after a month working in dr Camillo Ricordi’s Diabetes Research Institute in Miami, I started a large series of human islet isolation procedures in Leiden, and from september 1998 documenting the detailed GMP (‘Good Manufacturing Practice’) standard operating procedures, as well as ‘building’ our clinical islet isolation clean room with help from the Miami team in close cooperation with dr. Amon Wafelman (department of Clinical Pharmacy & Toxicology) managing the building of our brand new Interdivisional GMP-facility LUMC (IGFL) of six clean rooms and two chemical product laboratories – that was opened officially Feb 22, 2000 with the symposium, a film, and a tour in the GMP facility.
One year later the GMP islet facility was fully operational and summer 2001 we got a cautious green light (GMP license) for clinical transplantation of any high quality – approved – islet preparations.
Around the same time islet transplantation suddenly became very promising with ‘The Edmonton protocol’. However with the fast increase of logistic and financial demands, and reorganization between LUMC divisions it took till 2007 to finally start first transplants by an expanded islet team in the LUMC clinical islet center in Leiden.
Worldwide since 2000 several hundred people have received islet transplants that generally do not result in long term insulin independence , but do help sugar regulation in the transplant recipients.

Notes :
Links to some publications, news paper reports etc will follow later.

Updates:

Post updated with more details 20191215

Presentation ‘Isolation of Islets of Langerhans for Transplantation in Type-1 Diabetic Patients’ by Michel van der Burg, Feb 22, 2000 – Opening Symposium of the Interdivisional GMP facility of the Leiden University Medical Centre, Leiden, Netherlands. Film : 20191213 Michel van der Burg | miracles.media

Ductus Pancreaticus

① memo 20190503 ~ Ductus Pancreaticus ~ Human pancreas model with a ‘cut’ showing the pancreatic duct for drainage of the digestive pancreatic juice to the intestinal tract – this week in the Corpus museum in Oegstgeest near Leiden, Holland.
I used that pancreatic duct many years for (retrograde) infusion of digestive enzymes (mostly collagenase) in the pancreas to digest the connective tissue in the gland and release the’isolated’ islets of Langerhans for transplantion of purified islets aiming to cure diabetes .

25 Year Islet Transplants

July 3, 2014 – Holland, Leiden University Hospital, 25 years ago , short excerpt – highlighting the moment of transplanting – from the 19890613 surgery journal at our start of the first pre-clinical succesfull islets graft transplants in the Netherlands and most of Europe, using a simple yet very novel approach that eventually recently became the worldwide -usa at least- standard for transplanting clinical grade purified islets in insulin-dependent diabetic patients – link to article on the 25 year timeline of progress in research and patient treatment , here : http://www.cellr4.org/article/128 .

25 Year Islet Transplants | 20140703 | 1-memo.com