scholarly journals Advances in Pancreatic Islet Transplantation Sites for the Treatment of Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Fritz Cayabyab ◽  
Lina R. Nih ◽  
Eiji Yoshihara
Keyword(s):  
Graft Survival ◽  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Complex Disease ◽  
Blood Glucose Monitoring ◽  
Great Promise ◽  
Islet Graft ◽  
Pancreatic Islet Transplantation ◽  
Post Transplantation ◽  
Treatment Of Diabetes

Diabetes is a complex disease that affects over 400 million people worldwide. The life-long insulin injections and continuous blood glucose monitoring required in type 1 diabetes (T1D) represent a tremendous clinical and economic burdens that urges the need for a medical solution. Pancreatic islet transplantation holds great promise in the treatment of T1D; however, the difficulty in regulating post-transplantation immune reactions to avoid both allogenic and autoimmune graft rejection represent a bottleneck in the field of islet transplantation. Cell replacement strategies have been performed in hepatic, intramuscular, omentum, and subcutaneous sites, and have been performed in both animal models and human patients. However more optimal transplantation sites and methods of improving islet graft survival are needed to successfully translate these studies to a clinical relevant therapy. In this review, we summarize the current progress in the field as well as methods and sites of islet transplantation, including stem cell-derived functional human islets. We also discuss the contribution of immune cells, vessel formation, extracellular matrix, and nutritional supply on islet graft survival. Developing new transplantation sites with emerging technologies to improve islet graft survival and simplify immune regulation will greatly benefit the future success of islet cell therapy in the treatment of diabetes.

Current status of pancreatic islet transplantation

2006 ◽  
Vol 110 (6) ◽  
pp. 611-625 ◽  
Author(s):  
Shaheed Merani ◽  
A. M. James Shapiro
Keyword(s):  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Current Status ◽  
Small Subset ◽  
Type I ◽  
Pancreatic Islet Transplantation ◽  
Post Transplantation ◽  
Edmonton Protocol ◽  
Islet Transplants ◽  
Islet Survival

DM (diabetes mellitus) is a metabolic disorder of either absolute or relative insulin deficiency. Optimized insulin injections remain the mainstay life-sustaining therapy for patients with T1DM (Type I DM) in 2006; however, a small subset of patients with T1DM (approx. 10%) are exquisitely sensitive to insulin and lack counter-regulatory measures, putting them at higher risk of neuroglycopenia. One alternative strategy to injected insulin therapy is pancreatic islet transplantation. Islet transplantation came of age when Paul E. Lacy successfully reversed chemical diabetes in rodent models in 1972. In a landmark study published in 2000, Shapiro et al. [A. M. Shapiro, J. R. Lakey, E. A. Ryan, G. S. Korbutt, E. Toth, G. L. Warnock, N. M. Kneteman and R. V. Rajotte (2000) N. Engl. J. Med. 343, 230–238] reported seven consecutive patients treated with islet transplants under the Edmonton protocol, all of whom maintained insulin independence out to 1 year. Substantial progress has occurred in aspects of pancreas procurement, transportation (using the oxygenated two-layer method) and in islet isolation (with controlled enzymatic perfusion and subsequent digestion in the Ricordi chamber). Clinical protocols to optimize islet survival and function post-transplantation improved dramatically with the introduction of the Edmonton protocol, but it is clear that this approach still has potential limitations. Newer pharmacotherapies and interventions designed to promote islet survival, prevent apoptosis, to promote islet growth and to protect islets in the long run from immunological injury are rapidly approaching clinical trials, and it seems likely that clinical outcomes of islet transplantation will continue to improve at the current exponential pace.

scholarly journals Improved Baculovirus Vectors for Transduction and Gene Expression in Human Pancreatic Islet Cells

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 574 ◽  
Author(s):  
Leo Graves ◽  
Mine Aksular ◽  
Riyadh Alakeely ◽  
Daniel Ruiz Buck ◽  
Adam Chambers ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Pancreatic Islet Cells ◽  
Pancreatic Islet Transplantation ◽  
Post Transplantation ◽  
Safe Alternative ◽  
Human Pancreatic Islet

Pancreatic islet transplantation is a promising treatment for type 1 diabetes mellitus offering improved glycaemic control by restoring insulin production. Improved human pancreatic islet isolation has led to higher islet transplantation success. However, as many as 50% of islets are lost after transplantation due to immune responses and cellular injury, gene therapy presents a novel strategy to protect pancreatic islets for improved survival post-transplantation. To date, most of the vectors used in clinical trials and gene therapy studies have been derived from mammalian viruses such as adeno-associated or retrovirus. However, baculovirus BacMam vectors provide an attractive and safe alternative. Here, a novel BacMam was constructed containing a frameshift mutation within fp25, which results in virus stocks with higher infectious titres. This improved in vitro transduction when compared to control BacMams. Additionally, incorporating a truncated vesicular stomatitis virus G protein increased transduction efficacy and production of EGFP and BCL2 in human kidney (HK-2) and pancreatic islet β cells (EndoC βH3). Lastly, we have shown that our optimized BacMam vector can deliver and express egfp in intact pancreatic islet cells from human cadaveric donors. These results confirm that BacMam vectors are a viable choice for providing delivery of transgenes to pancreatic islet cells.

Pancreatic islet transplantation under the kidney capsule of mice: model of refinement for molecular and ex-vivo graft analysis

2021 ◽  
pp. 002367722110040
Author(s):  
Julien Thévenet ◽  
Valery Gmyr ◽  
Nathalie Delalleau ◽  
François Pattou ◽  
Julie Kerr-Conte
Keyword(s):  
Islet Transplantation ◽  
Pain Treatment ◽  
Ex Vivo ◽  
Well Being ◽  
Diabetic Patients ◽  
Mice Model ◽  
Pancreatic Islet Transplantation ◽  
Post Transplantation ◽  
Kidney Capsule

Diabetes cell therapy by human islet transplantation can restore an endogenous insulin secretion and normal glycaemic control in type 1 diabetic patients for as long as 10 years post transplantation. Before transplantation, each clinical islet preparation undergoes extensive in-vitro and in-vivo quality controls. The in-vivo quality control assay consists of transplanting human islets under the kidney capsule of immunocompromised mice. Currently, it is considered the best predictive factor to qualify clinical transplant efficiency. This chimeric model offers a wide area of study since it combines the possibility of producing not only quantitative but also a maximum of qualitative data. Today’s technological advances allow us to obtain more accurate and stronger data from the animals used in research while ensuring their comfort and well-being throughout the protocol, including cage enrichment and pain treatment during and after surgery. As demonstrated in this valuable model, we are able to generate more usable results (Refine), while reducing the number of animals used (Reduce), by focusing on the development of ex-vivo analysis techniques (Replace), which clearly highlights the Burch and Russell 3Rs concept.

A subcutaneous pancreatic islet transplantation platform using a clinically applicable, biodegradable Vicryl mesh scaffold ‐ an experimental study

2020 ◽  
Vol 33 (7) ◽  
pp. 806-818 ◽  
Author(s):  
Hirotake Komatsu ◽  
Nelson Gonzalez ◽  
Mayra Salgado ◽  
Colin A. Cook ◽  
Junfeng Li ◽  
...  
Keyword(s):  
Experimental Study ◽  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Pancreatic Islet Transplantation ◽  
Vicryl Mesh
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