217-OR: Islet Transplantation vs. Standard of Care for Type 1 Diabetes Complicated by Severe Hypoglycemia from the Collaborative Islet Transplant Registry (CITR) and T1D Exchange (T1DX) Registry

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 217-OR
Author(s):  
MICHAEL R. RICKELS ◽  
NICOLE C. FOSTER ◽  
CASSANDRA M. BALLOU ◽  
BERNHARD J. HERING ◽  
RODOLFO ALEJANDRO ◽  
...  
2018 ◽  
Vol 4 (11) ◽  
pp. e401 ◽  
Author(s):  
Melissa H. Lee ◽  
Glenn M. Ward ◽  
Richard J. MacIsaac ◽  
Kathy Howe ◽  
D. Jane Holmes-Walker ◽  
...  

2020 ◽  
Author(s):  
Braulio A Marfil-Garza ◽  
Joshua Hefler ◽  
Mario Bermudez De Leon ◽  
Rena Pawlick ◽  
Nidheesh Dadheech ◽  
...  

Abstract Regulatory T cells (Tregs) have become highly relevant in the pathophysiology and treatment of autoimmune diseases, such as type 1 diabetes (T1D). As these cells are known to be defective in T1D, recent efforts have explored ex vivo and in vivo Treg expansion and enhancement as a means for restoring self-tolerance in this disease. Given their capacity to also modulate alloimmune responses, studies using Treg-based therapies have recently been undertaken in transplantation. Islet transplantation provides a unique opportunity to study the critical immunological crossroads between auto- and alloimmunity. This procedure has advanced greatly in recent years, and reports of complete abrogation of severe hypoglycemia and long-term insulin independence have become increasingly reported. It is clear that cellular transplantation has the potential to be a true cure in T1D, provided the remaining barriers of cell supply and abrogated need for immune suppression can be overcome. However, the role that Tregs play in islet transplantation remains to be defined. Herein, we synthesize the progress and current state of Treg-based therapies in T1D and islet transplantation. We provide an extensive, but concise, background to understand the physiology and function of these cells and discuss the clinical evidence supporting potency and potential Treg-based therapies in the context of T1D and islet transplantation. Finally, we discuss some areas of opportunity and potential research avenues to guide effective future clinical application. This review provides a basic framework of knowledge for clinicians and researchers involved in the care of patients with T1D and islet transplantation.


2012 ◽  
Vol 94 (10S) ◽  
pp. 159 ◽  
Author(s):  
M. R. Rickels ◽  
T. Berney ◽  
P. Stock ◽  
P. A. Senior ◽  
R. Alejandro ◽  
...  

Diabetes Care ◽  
2018 ◽  
Vol 41 (5) ◽  
pp. 1001-1008 ◽  
Author(s):  
Eric D. Foster ◽  
Nancy D. Bridges ◽  
Irene D. Feurer ◽  
Thomas L. Eggerman ◽  
Lawrence G. Hunsicker ◽  
...  

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 84-85
Author(s):  
R Alejandro ◽  
B Hering ◽  
F Barton ◽  
M Appel ◽  
F Kandeel ◽  
...  

Author(s):  
Sophie Walker ◽  
Mahesh Appari ◽  
Shareen Forbes

Islet transplantation is a treatment for selected adults with Type 1 diabetes and severe hypoglycemia. Islets from two or more donor pancreases, a scarce resource, are usually required to impact on glycemic control but the treatment falls short of a cure. Islets are avascular when transplanted into the hypoxic liver environment and subjected to inflammatory insults, immune attack and toxicity from systemic immunosuppression. The Collaborative Islet Transplant Registry with outcome data on over 1000 islet transplant recipients has demonstrated that larger islet numbers transplanted and older age of recipient are associated with better outcomes. Induction with T cell depleting agents and the TNF-α inhibitor Etanercept and maintenance systemic immunosuppression with mTOR inhibitors in combination with calcineurin inhibitors also appear advantageous, but concerns remain over immunosuppressive toxicity. We discuss strategies and therapeutics which address specific challenges of islet transplantation, many of which are at the pre-clinical stage of development. On the horizon are adjuvant cell therapies with mesenchymal stromal cells and regulatory T cells that have been used in preclinical models and in humans in other contexts; such a strategy may enable reductions in immunosuppression in the early peri-transplant period when the islets are vulnerable to apoptosis. Human embryonic stem-cell derived islets are in early phase clinical trials and hold the promise of an inexhaustible supply of insulin producing cells; effective encapsulation of such cells or, silencing of the HLA complex would eliminate the need for immunosuppression, enabling this therapy to be used in all those with Type 1 diabetes.


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