scholarly journals Considerations and Challenges of Islet Transplantation and Future Therapies on the Horizon

2021 ◽  
Author(s):  
Sophie Walker ◽  
Mahesh Appari ◽  
Shareen Forbes
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Clinical Stage ◽  
Embryonic Stem ◽  
Outcome Data ◽  
Cell Therapies ◽  
Islet Transplant ◽  
Systemic Immunosuppression ◽  
Stage Of Development

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.

Progress in Translational Regulatory T Cell Therapies for Type 1 Diabetes and Islet Transplantation

2020 ◽  
Author(s):  
Braulio A Marfil-Garza ◽  
Joshua Hefler ◽  
Mario Bermudez De Leon ◽  
Rena Pawlick ◽  
Nidheesh Dadheech ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Ex Vivo ◽  
Severe Hypoglycemia ◽  
Cell Therapies ◽  
Current State ◽  
Cellular Transplantation ◽  
And Function

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.

scholarly journals Overview of Cellular Transplantation in Diabetes Mellitus: Focus on the Metabolic Outcome

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Livio Luzi ◽  
Stefano Benedini ◽  
Andrea Caumo ◽  
Ileana Terruzzi
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Islet Transplantation ◽  
Immunosuppressive Drugs ◽  
Cell Therapies ◽  
Cellular Transplantation ◽  
Major Disadvantage ◽  
Pancreas Islet

Diabetes mellitus is a metabolic disease possible to treat via several different therapeutic approaches. Since the advent of insulin in 1922, type 1 diabetes mellitus has become a chronic treatable disease. Nonetheless, type 1 diabetes mellitus can be a devastating disease when the macro- and microangiopathic complications take place after several years of illness. Starting from the eighties, pancreas/islet transplantation has become a potential innovative treatment of diabetes mellitus. The major advantage of pancreas/islet transplantation is the restoration of c-peptide cosecretion along with insulin; the major disadvantage is the need to administer immunosuppressive drugs which are diabetogenic themselves. Islet transplantation is the progenitor of more recent forms of cellular and stem cell therapies which will be reviewed herein. Cellular therapies for diabetes mellitus are still an experimental procedure. Herein we present the actual current achievements and an outlook of close future possible advancements in the area of cellular transplantation for the cure of diabetes mellitus.

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 ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Severe Hypoglycemia ◽  
Standard Of Care ◽  
Islet Transplant ◽  
Transplant Registry ◽  
Islet Transplant Registry

Ten‐years outcomes of islet transplantation in patients with type 1 diabetes: data from the Swiss‐French GRAGIL network

2021 ◽  
Author(s):  
Sandrine Lablanche ◽  
Sophie Borot ◽  
Anne Wojtusciszyn ◽  
Kristina Skaare ◽  
Alfred Penfornis ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation

Islet Transplantation on Biodegradable Polymer Scaffolds for Type 1 Diabetes in Syngeneic and Xenogeneic Murine Models

2011 ◽  
pp. P1-497-P1-497
Author(s):  
Romie F Gibly ◽  
Xiaomin Zhang ◽  
Dixon B Kaufman ◽  
William L Lowe ◽  
Lonnie D Shea
Keyword(s):  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Biodegradable Polymer ◽  
Murine Models ◽  
Polymer Scaffolds

scholarly journals The Future of Clinical Islet Transplantation in the United States

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Michael F Knoll ◽  
Carmela A Knoll ◽  
Rita Bottino ◽  
Massimo Trucco ◽  
Suzanne Bertera ◽  
...  
Keyword(s):  
Quality Of Life ◽  
United States ◽  
Type 1 Diabetes ◽  
Islet Transplantation ◽  
Drug Administration ◽  
The United States ◽  
Clinical Islet Transplantation ◽  
The World

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.

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