The Experts below are selected from a list of 17364 Experts worldwide ranked by ideXlab platform
Camillo Ricordi - One of the best experts on this subject based on the ideXlab platform.
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clinical pancreatic Islet Transplantation
Nature Reviews Endocrinology, 2017Co-Authors: A James M Shapiro, Marta Pokrywczynska, Camillo RicordiAbstract:Islet Transplantation has become a realistic treatment option for a subset of patients with type 1 diabetes mellitus. This Review outlines the techniques involved in the procedure, as well as the risks, long-term outcomes and advances in the care of patients after they have received an Islet transplant.
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autologous pancreatic Islet Transplantation for severe trauma
The New England Journal of Medicine, 2010Co-Authors: Rahul M Jindal, Camillo Ricordi, Craig D ShriverAbstract:To the Editor: Autologous pancreatic Islet Transplantation has been successfully carried out after total pancreatectomy for chronic pancreatitis, and allogeneic Islet-cell Transplantation has had limited success.1,2 We report a case of successful Islet Transplantation from the pancreas after total pancreatectomy because of trauma. A 21-year-old airman serving in a remote part of Afghanistan was hit by three high-velocity bullets on November 21, 2009, and was rapidly transferred to Walter Reed Army Medical Center. As part of needed rescue surgery, a portion of the stomach, the gallbladder, the entire duodenum, and the head of the pancreas were removed. In addition, . . .
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The clinical impact of Islet Transplantation.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2008Co-Authors: Paolo Fiorina, Camillo Ricordi, A. M. James Shapiro, Antonio SecchiAbstract:Islet cell Transplantation has recently emerged as one of the most promising therapeutic approaches to improving glycometabolic control in diabetic patients and, in many cases, achieving insulin independence. Unfortunately, many persistent flaws still prevent Islet Transplantation from becoming the gold standard treatment for type 1 diabetic patients. We review the state of the art of Islet Transplantation, outcomes, immunosuppression and—most important—the impact on patients' survival and long-term diabetic complications and eventual alternative options. Finally, we review the many problems in the field and the challenges to Islet survival after Transplantation. The rate of insulin independence 1 year after Islet cell Transplantation has significantly improved in recent years (60% at 1 year postTransplantation compared with 15% previously). Recent data indicate that restoration of insulin secretion after Islet cell Transplantation is associated with an improvement in quality of life, with a reduction in hypoglycemic episodes and potentially with a reduction in long-term diabetic complications. Once clinical Islet Transplantation has been successfully established, this treatment could even be offered to diabetic patients long before the onset of diabetic complications.
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Allogeneic Islet Transplantation
Expert opinion on biological therapy, 2007Co-Authors: S. Marzorati, Antonello Pileggi, Camillo RicordiAbstract:Significant progress has been made in the field of beta-cell replacement therapies by Islet Transplantation in patients with unstable Type 1 diabetes mellitus (T1DM). Recent clinical trials have shown that Islet Transplantation can reproducibly lead to insulin independence when adequate Islet numbers are implanted. Benefits include improvement of glycemic control, prevention of severe hypoglycemia and amelioration of quality of life. Numerous challenges still limit this therapeutic option from becoming the treatment of choice for T1DM. The limitations are primarily associated with the low Islet yield of human pancreas isolations and the need for chronic immunosuppressive therapies. Herein the authors present an overview of the historical progress of Islet Transplantation and outline the recent advances of the field. Cellular therapies offer the potential for a cure for patients with T1DM. The progress in beta-cell replacement treatment by Islet Transplantation as well as those of emerging immune interventions for the restoration of self tolerance justify great optimism for years to come.
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pancreatic Islet Transplantation for treating diabetes
Expert Opinion on Biological Therapy, 2006Co-Authors: Shinichi Matsumoto, Yukihide Yonekawa, Hirofumi Noguchi, Naoya Kobayashi, Teru Okitsu, Yasuhiro Iwanaga, Hideo Nagata, Camillo RicordiAbstract:Pancreatic Islet Transplantation is one of the options for treating diabetes and has been shown to improve the quality of life of severe diabetic patients. Since the Edmonton protocol was announced, Islet Transplantation have advanced considerably, including Islet after kidney Transplantation, utilisation of non-heart-beating donors, single-donor Islet Transplantation and living-donor Islet Transplantation. These advances were based on revised immunosuppression protocols, improved pancreas procurement and Islet isolation methods, and enhanced Islet engraftment. Further improvements are necessary to make Islet Transplantation a routine clinical treatment. To synergise efforts towards a cure for type 1 diabetes, a Diabetes Research Institute (DRI) Federation is currently being established to include leading diabetes research centres worldwide, including DRIs in Miami, Edmonton and Kyoto among others.
A. M. James Shapiro - One of the best experts on this subject based on the ideXlab platform.
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Biologic agents in Islet Transplantation.
Current diabetes reports, 2013Co-Authors: Boris Gala-lopez, Andrew R. Pepper, A. M. James ShapiroAbstract:Islet Transplantation is today an accepted modality for treating selected patients with frequent hypoglycemic events or severe glycemic lability. Despite tremendous progress in Islet isolation, culture, and preservation, clinical use is still restricted to a limited subset, and lifelong immunosuppression is required. Issues surrounding limited Islet revascularization and immune destruction remain. One of the major challenges is to prevent alloreactivity and recurrence of autoimmunity against β-cells. These two hurdles can be effectively reduced by immunosuppressive therapy combining induction and maintenance treatments. The introduction of highly potent and selective biologic agents has significantly reduced the frequency of acute rejection and has prolonged graft survival, while minimizing the complications of this therapeutic scheme. This review will address the most important biological agents used in Islet Transplantation. We provide a historical perspective of their introduction into clinical practice and their role in current clinical protocols, aiming at improved engraftment efficiency, increased long-term survival, and better overall results of clinical Islet Transplantation.
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State of the Art of Clinical Islet Transplantation and Novel Protocols of Immunosuppression
Current Diabetes Reports, 2011Co-Authors: A. M. James ShapiroAbstract:Clinical Islet Transplantation has transitioned from curiosity to realistic therapy over the past decade. An estimated 750 patients have undergone intraportal Islet-alone Transplantation over this period, and a smaller subset received combined Islet-kidney transplants. The primary benefit of successful Islet Transplantation has been to eliminate severe, recurrent hypoglycemia, a problem that has been hard to eliminate by other means in 15% of those with type 1 diabetes. The secondary benefit of independence from insulin has attracted patients, but has had limited sustainability previously, especially with a single-donor graft, but recent results from four independent centers suggest marked improvement in long-term outcome, with 5-year results now approximating solitary pancreas Transplantation. Emerging data confirm that Islet Transplantation can stabilize and reverse several secondary diabetic complications similar to whole pancreas Transplantation, but larger, head-to-head trials are needed to compare Islet Transplantation with best medical therapies. Current goals are to extend durability, and to make Islet Transplantation more widely available for patients in need. Governmental and health insurance providers in several countries now reimburse Islet Transplantation as part of clinical care. As the safety of the procedure and of adjunctive immunosuppressive therapies improve, and benefit accrues over potential risk, Islet Transplantation will be offered earlier in the course of the disease, including newly diagnosed children. The role of Islet Transplantation in type 2 diabetes has yet to be defined. We review the current status of Islet Transplantation, and discuss current and future immunosuppressive protocols that will pave the way to more broad application of cellular replacement in diabetes.
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Role of Imaging in Clinical Islet Transplantation
Radiographics, 2010Co-Authors: Nassrein Hussein, Richard J. Owen, Vimal Patel, Ravi Bhargava, Christian Toso, A. M. James ShapiroAbstract:Islet Transplantation is an innovative and effective clinical strategy for patients with type 1 diabetes whose clinical condition is inadequately managed even with the most aggressive medical treatment regimens. In Islet Transplantation, purified Islets extracted from the pancreas of deceased donors are infused into the portal vein of the recipient liver. Engrafted Islets produce insulin and thus restore euglycemia in many patients. After Islet Transplantation performed with the original Edmonton protocol, 80% of patients were insulin independent at 1 year and approximately 20% were insulin independent at 5 years. With more recent technical advances, 50% of patients or more maintain insulin independence 5 years after Islet Transplantation. The success rate with single-donor Islet infusions has markedly improved over time. Even in patients who lose insulin independence, Islet Transplantation is considered successful because it provides improved glycemic control and a higher quality of life. Imaging plays an important role in Islet Transplantation and is routinely used to evaluate potential recipients, guide the Transplantation process, and monitor patients for postTransplantation complications. Because of the success of Islet Transplantation and its increasing availability worldwide, familiarity with the role of imaging is important.
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The clinical impact of Islet Transplantation.
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2008Co-Authors: Paolo Fiorina, Camillo Ricordi, A. M. James Shapiro, Antonio SecchiAbstract:Islet cell Transplantation has recently emerged as one of the most promising therapeutic approaches to improving glycometabolic control in diabetic patients and, in many cases, achieving insulin independence. Unfortunately, many persistent flaws still prevent Islet Transplantation from becoming the gold standard treatment for type 1 diabetic patients. We review the state of the art of Islet Transplantation, outcomes, immunosuppression and—most important—the impact on patients' survival and long-term diabetic complications and eventual alternative options. Finally, we review the many problems in the field and the challenges to Islet survival after Transplantation. The rate of insulin independence 1 year after Islet cell Transplantation has significantly improved in recent years (60% at 1 year postTransplantation compared with 15% previously). Recent data indicate that restoration of insulin secretion after Islet cell Transplantation is associated with an improvement in quality of life, with a reduction in hypoglycemic episodes and potentially with a reduction in long-term diabetic complications. Once clinical Islet Transplantation has been successfully established, this treatment could even be offered to diabetic patients long before the onset of diabetic complications.
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Progress in Islet Transplantation in Patients with Type 1 Diabetes Mellitus
Treatments in Endocrinology, 2006Co-Authors: Wayne Truong, A. M. James ShapiroAbstract:More than 500 patients with type 1 diabetes mellitus have now received Islet transplants at over 50 institutions worldwide in the past 5 years. Rates of insulin independence at 1 year with current protocols are impressive. However, inexorable decay of Islet function over time indicates that there are many opportunities for improvement. Improved control of glycosylated hemoglobin and reduced risk of recurrent hypoglycemia are seen as important benefits of Islet Transplantation, irrespective of the status regarding insulin independence. For the use of Islet Transplantation to expand it is essential that the donor-to-recipient ratio be reliably reduced to 1:1. Enormous opportunities lie ahead for the development of successful living donor Islet Transplantation, single donor protocols, improved engraftment, Islet proliferation in vitro and in the recipient, alternative Islet sources, and novel tolerizing drugs. With these emerging opportunities, Islet Transplantation may expand to include more patients with type 1 diabetes, including children, and will not be restricted to the most unstable forms of the disease, as it is today.
A James M Shapiro - One of the best experts on this subject based on the ideXlab platform.
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regulated cell death seen through the lens of Islet Transplantation
Cell Transplantation, 2018Co-Authors: Antonio Bruni, Stefan R Bornstein, Andreas Linkermann, A James M ShapiroAbstract:Clinical Islet Transplantation effectively restores euglycemia and corrects glycosylated hemoglobin in labile type 1 diabetes mellitus (T1DM). Despite marked improvements in Islet Transplantation outcomes, acute Islet cell death remains a substantial obstacle that compromises long-term engraftment outcomes. Multiple organ donors are routinely required to achieve insulin independence. Therapeutic agents that ameliorate cell death and/or control injury-related inflammatory cascades offer potential to improve Islet transplant success. Apoptotic cell death has been identified as a major contributor to cellular demise and therapeutic strategies that subvert initiation and consequences of apoptotic cell death have shown promise in pre-clinical models. Indeed, in numerous pathologies and diseases apoptosis has been the most extensively described form of regulated cell death. However, recent identification of novel, alternative regulated cell death pathways in other disease states and solid organ Transplantation suggest that these additional pathways may also have substantial relevance in Islet Transplantation. These regulated, non-apoptotic cell death pathways exhibit distinct biochemical characteristics but have yet to be fully characterized within Islet Transplantation. We review herein the various regulated cell death pathways and highlight their relative potential contributions to Islet viability, engraftment failure and Islet dysfunction.
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clinical pancreatic Islet Transplantation
Nature Reviews Endocrinology, 2017Co-Authors: A James M Shapiro, Marta Pokrywczynska, Camillo RicordiAbstract:Islet Transplantation has become a realistic treatment option for a subset of patients with type 1 diabetes mellitus. This Review outlines the techniques involved in the procedure, as well as the risks, long-term outcomes and advances in the care of patients after they have received an Islet transplant.
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current status of pancreatic Islet Transplantation
Clinical Science, 2006Co-Authors: Shaheed Merani, A James M ShapiroAbstract: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.
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advances in pancreatic Islet Transplantation in humans
Diabetes Obesity and Metabolism, 2006Co-Authors: Sulaiman A Nanji, A James M ShapiroAbstract:With recent advances in methods of Islet isolation and the introduction of more potent and less diabetogenic immunosuppressive therapies, Islet Transplantation has progressed from research to clinical reality. Presently, several international centres have demonstrated successful clinical outcomes with high rates of insulin independence after Islet Transplantation. Ongoing refinements in donor pancreas procurement and processing, developments in Islet isolation and purification technology, and advances in novel immunological conditioning and induction therapies have led to the acceptance of Islet Transplantation as a safe and effective therapy for patients with type 1 diabetes. This review provides a historical perspective of Islet Transplantation, outlines the recent advances and current clinical outcomes, and addresses the present challenges and future directions in clinical Islet Transplantation.
Norma S. Kenyon - One of the best experts on this subject based on the ideXlab platform.
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Requirements for success in clinical Islet Transplantation.
Transplantation, 2005Co-Authors: Camillo Ricordi, Luca Inverardi, Norma S. Kenyon, Federico Bertuzzi, John A. Goss, Rodolfo AlejandroAbstract:A few groups have endured the challenges of time, anecdotal success stories, logistic and funding impediments, to bring the field of clinical Islet Transplantation where it stands today. The recent improvement in clinical results has paralleled a renewed interest in Islet Transplantation and an increasing number of centers have entered the field. Selected institutions have now clearly demonstrated that insulin independence can be a reproducible and achievable goal. Other centers struggle with mixed results, while occasional early failures of Islet transplants are still observed. This center effect underlines not just a learning curve, but also the complexity of the approach, which requires multidisciplinary expertise and attention to critical variables that need to be closely monitored to assure adequate clinical outcomes. The future success and large scale applicability of Islet Transplantation will rely on the synergistic research progress in critical areas that contribute to the sequential and integrated approach required for success in clinical Islet Transplantation.
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Islet Transplantation: immunological perspectives.
Current opinion in immunology, 2003Co-Authors: Luca Inverardi, Norma S. Kenyon, Camillo RicordiAbstract:Clinical trials of Islet Transplantation are showing remarkable success, but they require administration of chronic immunosuppression, and are underscoring the large gap that exists between the number of human donors available and the number of patients that could benefit from the procedure. Recent progress has been made in the definition of key immunological mechanisms that are involved in determining Islet transplant outcome. Clinical and preclinical studies, and studies in small animal model systems, will all eventually contribute to the definition of efficient and safe protocols for Islet Transplantation. If the use of xenografts is successful, it might represent a solution to the shortage of human organs.
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Alternatives to immunosuppressive drugs in human Islet Transplantation
Current diabetes reports, 2002Co-Authors: Alison Anne Cotterell, Norma S. KenyonAbstract:Although intensive insulin therapy has resulted in improved metabolic control and decreases in the incidence of complications, the occurrence of severe hypoglycemia remains an issue, as does the continued potential for complications. Islet Transplantation, a promising treatment for type 1 diabetes, has been shown to improve blood sugar levels and decrease or even abrogate the incidence of hypoglycemia. The lack of tissue availability and the toxic effects of immunosuppressants, however, limit the application of Islet Transplantation as a cure for diabetes. This article discusses possible alternatives to immunosuppressive drugs in human Islet Transplantations.
Luca Inverardi - One of the best experts on this subject based on the ideXlab platform.
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Requirements for success in clinical Islet Transplantation.
Transplantation, 2005Co-Authors: Camillo Ricordi, Luca Inverardi, Norma S. Kenyon, Federico Bertuzzi, John A. Goss, Rodolfo AlejandroAbstract:A few groups have endured the challenges of time, anecdotal success stories, logistic and funding impediments, to bring the field of clinical Islet Transplantation where it stands today. The recent improvement in clinical results has paralleled a renewed interest in Islet Transplantation and an increasing number of centers have entered the field. Selected institutions have now clearly demonstrated that insulin independence can be a reproducible and achievable goal. Other centers struggle with mixed results, while occasional early failures of Islet transplants are still observed. This center effect underlines not just a learning curve, but also the complexity of the approach, which requires multidisciplinary expertise and attention to critical variables that need to be closely monitored to assure adequate clinical outcomes. The future success and large scale applicability of Islet Transplantation will rely on the synergistic research progress in critical areas that contribute to the sequential and integrated approach required for success in clinical Islet Transplantation.
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Islet Transplantation: immunological perspectives.
Current opinion in immunology, 2003Co-Authors: Luca Inverardi, Norma S. Kenyon, Camillo RicordiAbstract:Clinical trials of Islet Transplantation are showing remarkable success, but they require administration of chronic immunosuppression, and are underscoring the large gap that exists between the number of human donors available and the number of patients that could benefit from the procedure. Recent progress has been made in the definition of key immunological mechanisms that are involved in determining Islet transplant outcome. Clinical and preclinical studies, and studies in small animal model systems, will all eventually contribute to the definition of efficient and safe protocols for Islet Transplantation. If the use of xenografts is successful, it might represent a solution to the shortage of human organs.
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Tolerance and pancreatic Islet Transplantation.
Philosophical transactions of the Royal Society of London. Series B Biological sciences, 2001Co-Authors: Luca Inverardi, Camillo RicordiAbstract: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.
