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 .

Human Islet Purification Miami 1998 • 20181102

Efficacy of the novel iodixanol-UWS density gradient for human islet purification

Slideshow (video) of my January 1999 oral presentation in Igls (Innsbruck), Austria, at the 18th Workshop of the AIDSPIT (Artificial Insulin Delivery Systems, Pancreas and Islet Transplantation) Study Group. (Now known as AIDPIT).

These results of this innovative islet purification method developed in our Leiden islet laboratory (LUMC) were the outcome of work I had done spring 1998 with the islet group of Camillo Ricordi in the “fast track” center for diabetes research at the Diabetes Research Institute in Miami , Florida, USA.

Notes

The slideshow (pdf) was first uploaded Nov. 11, 2010 at at Scribd , and Archive.org • URL http://archive.org/details/EfficacyOfTheNovelIodixanol-uwsDensityGradientForHumanIslet

Original video title (file name) : 20181102 ~ Human Islet Purification Miami 1998

Updates:
20241202 – Text updated with extra info. Youtube video in post replaced by Vimeo edition. Copied 1-memo post to michelvanderburg.com .

Citation info : Human Islet Purification Miami 1998 • Michel van der Burg • Miracles.Media • 20181102 • URL michelvanderburg.com/2018/11/02/ • TakeNode 3f2ec4d2-afe0-4580-b055-92a2f231a4fa

Lessons From Clinical Islet Transplantation


① memo 20170208 ~ Lessons From Clinical Islet Transplantation ~ Chairman K. Federlin (Giessen, Germany) opened the seminar Tuesday, January 25, 1994 and David Scharp started with his lessons from the Center in St. Louis (USA) – 13th Workshop of the AIDSPIT Study Group , Igls, Austria ( note : sound re-recorded from speaker of Olympus mini-tape dictaphone )

24th AIDPIT Workshop – Igls

① memo 20160125 ~ The 24th Workshop of the AIDPIT Study Group ~ Jan 25th 2005 at the 24th Workshop of the AIDPIT Study Group ~ Congress park , Igls (Innsbruck) Austria ~ ( AIDPIT : Artificial Insulin Delivery, Pancreas and Islet Transplantation ) ~ further details described in film below …

 

Out Of Service | 20140911

Out Of Service | 20140911 | 1-memo•com | In the morning of 9/11 2001 logistics forced me to officially announce a temporarily – 1 week – ‘out of service’ of our Leiden islet isolation and transplant center. Our center was started earlier that summer of 2001 at the Leiden University Medical Center. So, I decided to have a short vacation abroad – heaven, after being on call 24/7 almost non stop for years. Later that day at home, I was downstairs watching TV — because upstairs near my workroom the central heating was being replaced – when I saw the CNN breaking news about the plane crashing into the World Trade Center. That day would become a landmark in history and the course of my life.

Background image : Microscopy picture I took of purified human Islets of Langerhans – tiny clumps (size around 1/10 mm or 1/25 inch) of 10s to 1000s of cells that produce hormones like insulin – these cells are just visible when you enlarge this 50x microscopy picture : as tiny translucent ‘balls’ or ‘spheres’. The red color is from a stain that binds to the insulin cells.
Iodixanol-UWS purified human islets, stained with dithizone. Original magnification 50x.

Title: mvdb20041118_114555m0400.tif
Creator: Michael P.M. van der Burg
Caption/Description: Iodixanol-UWS purified human islets, stained with dithizone. Original magnification 50x. Copyright Notice: Copyright © 2004 M.P.M. van der Burg. All rights reserved. Digital Creation Date: 18 Nov 2004

References

Image published in : Transplantatie van eilandjes van Langerhans bij patiënten met diabetes mellitus type 1. Ned Tijdschr Geneeskd 2005 1 januari;149(1) – URL https://www.ntvg.nl/system/files/publications/2005100120001a.pdf

Efficacy of the novel iodixanol-UWS density gradient for human islet purification (Presentation publ. Archive Org – michelvanderburg, 19990125 )
https://archive.org/details/EfficacyOfTheNovelIodixanol-uwsDensityGradientForHumanIslet

25 Years of the Ricordi Automated Method for Islet Isolation. Piemonti L, Pileggi A. in CellR4 2013; 1(1): e128. – URL https://www.cellr4.org/article/128

Credit : Out Of Service | 20140911 | 1-memo•com | TakeNode ID e22f209c-14da-40d8-b11a-74a29b1e80b4

TAGS #michelvanderburg #1Memo #oncall #LeidenUniversity #OutOfService #Islet #Langerhans #isolation #purification #transplantation #clinic #human #center #diabetes #CNN #WorldTradeCenter #breakingnews #crash #CV #LUMC #microscopy #dithizone #stain #cell #insulin #therapy #Iodixanol #UWS #UniversityofWisconsin #solution

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