Islet of Langerhans Transplantation for the Treatment of Type 1 Diabetes

Swiss Surgery ◽  
2003 ◽  
Vol 9 (5) ◽  
pp. 242-246 ◽  
Author(s):  
Bucher ◽  
Mathe ◽  
Bosco ◽  
Andres ◽  
Bühler ◽  
...  

Islet of Langerhans transplantation is gaining recognition as a therapy for type 1 diabetes. The procedure involves enzymatic digestion of the pancreatic tissue, purification of the islets from the exocrine tissue, infusion of the islets into the portal vein and implantation in the liver. Until 1999, an overall rate of insulin independence of 14% at one year was reported in the International Islet Transplant Registry. The results of the "Edmonton protocol" since 2000 were a breakthrough in the field, with reports of 80% insulin independence at 1-year after solitary islet transplantation in non uremic patients with brittle type 1 diabetes. A rapamycin-based, steroid-free, islet-sparing immunosuppressive regimen was designed and the problem of the insufficient islet mass was tackled by sequential infusions of islets isolated from at least two pancreata. The University of Geneva has been involved in clinical islet transplantation since 1992, and has performed 51 allogeneic and 17 autologous. Twenty-one patients have been transplanted in Geneva since 2002. They were five solitary islet transplants, 14 islet after kidney transplants and two simultaneous islet-kidney (SIK) recipients. Insulin independence was achieved in 67%.

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Michael F Knoll ◽  
Carmela A Knoll ◽  
Rita Bottino ◽  
Massimo Trucco ◽  
Suzanne Bertera ◽  
...  

Clinical islet transplantation was first realized over four decades ago at the University of Minnesota. Autologous islet transplantation is now widely recognized as a treatment to prevent diabetes in patients after pancreas excision and is offered at major transplant centers throughout the United States and the world. Type 1 diabetes represents a much larger demographic in which islet transplantation may benefit patients. Allogeneic islet transplantation can now offer similar outcomes to pancreas transplantation in a subset of patients with labile type 1 diabetes with less risk than whole organ transplantation. It is recognized as a standard of care in nations around the world but not in the United States, despite the important developmental role US scientists and physicians have played. Early reports of islet transplantation focused on insulin independence that proved to diminish over time. However, regardless of insulin status, islet transplantation provides benefits ranging from improved quality of life to reduction in diabetic complications. A National Institutes of Health sponsored multi-center Phase 3 Clinical Trial (CIT-07) demonstrated safety and efficacy, although the Food and Drug Administration chose to consider islets as a biologic that requires licensure, which makes offering the procedure in the clinic very challenging. Until regulations can be brought into communion with international standards, allogeneic islet transplantation in the United States is unlikely to match international levels of success and once promising programs are left to wither on the vine. Food and Drug Administration approval would open the door for third party medical reimbursement and allow many patients the opportunity to enjoy better health and quality of life. Establishment of clinical islet transplantation for type 1 diabetes would lead to optimizations in procedures making it more efficacious and cost effective while offering support for ongoing islet xenotransplantation studies that could bring islet transplantation to even more patients.


2006 ◽  
Vol 184 (5) ◽  
pp. 221-225 ◽  
Author(s):  
Philip J O’Connell ◽  
Wayne J Hawthorne ◽  
Brian J Nankivell ◽  
Anita T Patel ◽  
Stacey N Walters ◽  
...  

2015 ◽  
Vol 173 (5) ◽  
pp. R165-R183 ◽  
Author(s):  
Mohsen Khosravi-Maharlooei ◽  
Ensiyeh Hajizadeh-Saffar ◽  
Yaser Tahamtani ◽  
Mohsen Basiri ◽  
Leila Montazeri ◽  
...  

Over the past decades, tremendous efforts have been made to establish pancreatic islet transplantation as a standard therapy for type 1 diabetes. Recent advances in islet transplantation have resulted in steady improvements in the 5-year insulin independence rates for diabetic patients. Here we review the key challenges encountered in the islet transplantation field which include islet source limitation, sub-optimal engraftment of islets, lack of oxygen and blood supply for transplanted islets, and immune rejection of islets. Additionally, we discuss possible solutions for these challenges.


2012 ◽  
Vol 12 (6) ◽  
pp. 1576-1583 ◽  
Author(s):  
M. D. Bellin ◽  
F. B. Barton ◽  
A. Heitman ◽  
J. V. Harmon ◽  
R. Kandaswamy ◽  
...  

2006 ◽  
Vol 67 (4) ◽  
pp. 909-913 ◽  
Author(s):  
Helena Miszta-Lane ◽  
Mohammadreza Mirbolooki ◽  
A.M. James Shapiro ◽  
Jonathan R.T. Lakey

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 139-OR
Author(s):  
ANNA LAM ◽  
KATHRYN J. POTTER ◽  
SHAREEN FORBES ◽  
SHARLEEN IMES ◽  
ANDREW J. MALCOLM ◽  
...  

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Preeti Chhabra ◽  
Kenneth L Brayman ◽  

Clinical islet allotransplantation represents a minimally invasive, efficacious alternative to pancreas transplantation for restoring glycemic control and insulin independence in select patients with type 1 diabetes that is complicated by intractable impaired hypoglycemia awareness and/or severe hypoglycemic events refractory to stabilization by other means. Over the last decade, islet transplantation outcomes have steadily improved in part due to refinements in the selection of optimal donors, islet isolation techniques, safer engraftment methods, and effective immunomodulatory and anti-inflammatory therapies. Insulin independence rates at five years post-transplantation at select centers have reached parity with pancreas alone transplantation, and marked progress has been achieved in islet transplantation outcomes using single-donor pancreas. However, widespread application of the procedure is still hindered due to a limited supply of donor pancreases, inadequate engraftment, and the harmful side effects of chronic immunosuppression. Strategies to address some of these challenges involve the use of alternative sources of beta cells or islets, extrahepatic sites of implantation, encapsulation of islets and novel therapies to induce tolerance. While several countries have now transitioned islet transplantation from experimental status to a funded clinical cure for patients with brittle type 1 diabetes that cannot be stabilized by more conventional means, in the US it still awaits regulatory approval and a financial mechanism for sustainable reimbursement. This review details the history and the current status of clinical islet allotransplantation while summarizing improvements that have been made in techniques involving isolation, purification, culture and assessment of human islets as well as the islet transplantation process itself. Furthermore, it discusses the limitations encountered that prevent its widespread application, strategies that address those limitations, and last but not least, clinical trials being conducted that will help position islet transplantation as a mainstay treatment for the cure of type 1 diabetes.


2014 ◽  
Vol 98 (9) ◽  
pp. 1007-1012 ◽  
Author(s):  
David P. Al-Adra ◽  
Richdeep S. Gill ◽  
Sharleen Imes ◽  
Doug O’Gorman ◽  
Tatsuya Kin ◽  
...  

2009 ◽  
Vol 9 (2) ◽  
pp. 419-423 ◽  
Author(s):  
T. Berney ◽  
S. Ferrari-Lacraz ◽  
L. Bühler ◽  
J. Oberholzer ◽  
N. Marangon ◽  
...  

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