Islet Transplantation
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JCI Insight ◽  
2022 ◽  
Jessica D. Kepple ◽  
Jessie M. Barra ◽  
Martin E. Young ◽  
Chad S. Hunter ◽  
Hubert M. Tse

2022 ◽  
Vol Publish Ahead of Print ◽  
Casey Ward ◽  
Jon S. Odorico ◽  
Michael R. Rickels ◽  
Thierry Berney ◽  
George W. Burke ◽  

2022 ◽  
Vol 12 (1) ◽  
Naoaki Sakata ◽  
Gumpei Yoshimatsu ◽  
Kiyoshi Chinen ◽  
Ryo Kawakami ◽  
Shohta Kodama

AbstractAlthough islet transplantation (ITx) is a promising therapy for severe diabetes mellitus, further advancements are necessary. Adiponectin, an adipokine that regulates lipid and glucose metabolism, exerts favorable effects on islets, such as reinforcement of the insulin-releasing function. This study evaluated the possibility of adiponectin use to improve ITx outcomes. We treated mouse islets with 10 µg/mL recombinant mouse adiponectin by overnight culture and then assessed the insulin-releasing, angiogenic, and adhesion functions of the islets. Furthermore, 80 syngeneic islet equivalents with or without adiponectin treatment were transplanted into the renal subcapsular space of diabetic mice. In in vitro assessment, released insulin at high glucose stimulation, insulin content, and expressions of vascular endothelial growth factor and integrin β1 were improved in adiponectin-treated islets. Furthermore, adiponectin treatment improved the therapeutic effect of ITx on blood glucose levels and promoted angiogenesis of the transplanted islets. However, the therapeutic effect was not pronounced in glucose tolerance test results. In conclusion, adiponectin treatment had preferable effects in the insulin-releasing, angiogenic, and adhesion functions of islets and contributed to the improvement of ITx. The future use of adiponectin treatment in clinical settings to improve ITx outcomes should be investigated.

2022 ◽  
Vol 23 ◽  
Rachel P. Tindall ◽  
Suzanne Bertera ◽  
Tadahiro Uemura ◽  
Molly Vincent ◽  
Michael F. Knoll ◽  

2022 ◽  
Vol 12 ◽  
Piotr Witkowski ◽  
Louis H. Philipson ◽  
John B. Buse ◽  
R. Paul Robertson ◽  
Rodolfo Alejandro ◽  

Clinical islet allotransplantation has been successfully regulated as tissue/organ for transplantation in number of countries and is recognized as a safe and efficacious therapy for selected patients with type 1 diabetes mellitus. However, in the United States, the FDA considers pancreatic islets as a biologic drug, and islet transplantation has not yet shifted from the experimental to the clinical arena for last 20 years. In order to transplant islets, the FDA requires a valid Biological License Application (BLA) in place. The BLA process is costly and lengthy. However, despite the application of drug manufacturing technology and regulations, the final islet product sterility and potency cannot be confirmed, even when islets meet all the predetermined release criteria. Therefore, further regulation of islets as drugs is obsolete and will continue to hinder clinical application of islet transplantation in the US. The Organ Procurement and Transplantation Network together with the United Network for Organ Sharing have developed separately from the FDA and BLA regulatory framework for human organs under the Human Resources & Services Administration to assure safety and efficacy of transplantation. Based on similar biologic characteristics of islets and human organs, we propose inclusion of islets into the existing regulatory framework for organs for transplantation, along with continued FDA oversight for islet processing, as it is for other cell/tissue products exempt from BLA. This approach would reassure islet quality, efficacy and access for Americans with diabetes to this effective procedure.

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.

Biomaterials ◽  
2021 ◽  
pp. 121342
Sean M. Kinney ◽  
Krystal Ortaleza ◽  
Alexander E. Vlahos ◽  
Michael V. Sefton

2021 ◽  
Vol 12 (4) ◽  
pp. 68
Armin Mooranian ◽  
Melissa Jones ◽  
Corina Mihaela Ionescu ◽  
Daniel Walker ◽  
Susbin Raj Wagle ◽  

Pancreatic β-cell loss and failure with subsequent deficiency of insulin production is the hallmark of type 1 diabetes (T1D) and late-stage type 2 diabetes (T2D). Despite the availability of parental insulin, serious complications of both types are profound and endemic. One approach to therapy and a potential cure is the immunoisolation of β cells via artificial cell microencapsulation (ACM), with ongoing promising results in human and animal studies that do not depend on immunosuppressive regimens. However, significant challenges remain in the formulation and delivery platforms and potential immunogenicity issues. Additionally, the level of impact on key metabolic and disease biomarkers and long-term benefits from human and animal studies stemming from the encapsulation and delivery of these cells is a subject of continuing debate. The purpose of this review is to summarise key advances in this field of islet transplantation using ACM and to explore future strategies, limitations, and hurdles as well as upcoming developments utilising bioengineering and current clinical trials.

2021 ◽  
Vol 105 (12S1) ◽  
pp. S47-S48
Eimear Wallace ◽  
Tapas Mitra ◽  
Lucien H. J. Schreiber ◽  
Giulia Lattinizi ◽  
Gabriella Bellavia ◽  

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