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 Tolerance and pancreatic islet transplantation

2001 ◽  
Vol 356 (1409) ◽  
pp. 759-765 ◽  
Author(s):  
Luca Inverardi ◽  
Camillo Ricordi
Keyword(s):  
Diabetes Mellitus ◽  
Islet Transplantation ◽  
Type I Diabetes ◽  
Immunological Tolerance ◽  
Type I Diabetes Mellitus ◽  
Current Status ◽  
Type I ◽  
Pancreatic Islet Transplantation ◽  
Term Survival

Islet transplantation holds renewed promise as a cure for type I diabetes mellitus. Results of recent clinical trials have shown remarkable success, and have reignited universal optimism for this procedure. In spite of this success, the need for life–long immunosuppression of the recipient still limits islet transplantation to patients with poorly controlled diabetes or to those requiring kidney transplantation. It is obvious that the achievement of immunological tolerance would broaden the indication for islet transplantation to a much larger cohort of patients with type I diabetes mellitus, most likely preventing long–term complications and contributing to a much improved quality of life. Increased understanding of the basic mechanisms of tolerance induction has resulted in the implementation of numerous experimental approaches to achieve long–term survival of islet grafts in the absence of chronic immunosuppression. In this brief review we will attempt to summarize the current status of research and knowledge.

scholarly journals Hemoglobin A1C Percentage in Nonhuman Primates: A Useful Tool to Monitor Diabetes before and after Porcine Pancreatic Islet Xenotransplantation

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Marco Marigliano ◽  
Anna Casu ◽  
Suzanne Bertera ◽  
Massimo Trucco ◽  
Rita Bottino
Keyword(s):  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Hemoglobin A1c ◽  
Diabetes Research ◽  
Pancreatic Islet Transplantation ◽  
Porcine Islet ◽  
Islet Xenotransplantation ◽  
Before And After ◽  
Islet Transplants ◽  
Diabetes Induction

Non-human primates (NHPs) are a very valuable experimental model for diabetes research studies including experimental pancreatic islet transplantation. In particular NHPs are the recipients of choice to validate pigs as possible source of pancreatic islets. The aim of this study was to quantify glycated hemoglobin percentage in NHPs and to assess whether changes in values reflect the metabolic trends after diabetes induction and islet transplantation. Sera from 15 NHPs were analyzed. 9 NHPs were rendered diabetic with streptozotocin (STZ), and 3 of them received porcine islet transplants. Hemoglobin A1c (HbA1c) percentage was measured with an assay based on a latex immunoagglutination inhibition methodology. Whereas diabetes and its duration were associated with increasing HbA1c levels, postislet transplantation blood glucose normalization was paralleled by a decrease in the HbA1c percentage. Our data provide evidence that HbA1c is a useful tool to monitor glucose metabolism in NHPs.

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.

Microfluidics for Live-Cell Imaging Pancreatic Islets of Langerhans for Human Transplant

2014 ◽  
Author(s):  
Joshua E. Mendoza-Elias ◽  
José Oberholzer ◽  
Yong Wang
Keyword(s):  
Islet Transplantation ◽  
Pancreatic Islet ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Islet Cells ◽  
Live Cell ◽  
Cell Physiology ◽  
Type I ◽  
Pancreatic Islet Transplantation ◽  
Β Cell

Since the introduction of the Edmonton Protocol in 2000, islet transplantation has been emerging as promising therapy for Type I diabetes mellitus (T1DM) and currently is the only therapy that can achieve glycemic control without the need for exogenous insulin. Transplanting islet cells has several advantages over transplanting a whole pancreas in that it involves only a minor surgical procedure with low morbidity and mortality, and at a significantly lower cost. However, an obstacle to realizing this goal is a lack of an islet potency index as required by the U.S. Food and Drug Administration (FDA) biologics licensing, as well as a more complete understanding of the physiological mechanisms governing islet and β-cell physiology. Recently, the University of Illinois at Chicago (UIC) has developed a microfluidic platform that can mimic in vivo islet microenvironments through precise and dynamic control of perifusing culture media and oxygen culture levels; all while measuring functionally relevant factors including intracellular calcium levels, mitochondrial potentials, and insulin secretion. By developing an understanding of the physiology and pathophysiology of islets we can more effectively develop strategies that reduce metabolic stress and promote optimization in order to achieve improved success of islet transplantation and open new clinical avenues. The presentation begins by introducing key issues in the field of pancreatic islet transplantation as a clinical therapy for T1DM. This is followed by brief review various technologies that have been developed to study islet cells. The presentation then describes the design, application, and evolution of UIC’s microfluidic-based multimodal islet perifusion and live-cell imaging system for the study of pancreatic islet and β-cell physiology. The article then concludes presenting initial findings from studies seeking to develop an islet potency test.

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.

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