The Experts below are selected from a list of 318 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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Lack of cytomegalovirus transmission after Pancreatic Islet Transplantation.
Cell Transplantation, 2020Co-Authors: Neal R. Barshes, Camillo Ricordi, F. Charles Brunicardi, Amy Mote, A. Paige Schock, Rodolfo Alejandro, John A. GossAbstract:In spite of antiviral prophylaxis, the transmission rate of cytomegalovirus (CMV) after solid organ Transplantation remains high. In contrast, CMV transmission has never been reported following Pancreatic Islet Transplantation (PIT). Eleven (seven CMV seronegative, four CMV seropositive) recipients underwent a total of 26 PITs. Following PIT recipients were monitored clinically and tested monthly for CMV antigenemia. Valganciclovir was given to all patients for 100 days after each PIT. Follow-up ranged from 6 to 24 months (median 14.5 months). Pancreatic Islet grafts were procured from 18 CMV seropositive and 8 seronegative donors (69% and 31% of donors, respectively). In total there were 6 R+D+, 3 R+D-, 12 R-D+, and 5 R-D-PITs. No patient developed CMV antigenemia or symptoms consistent with CMV infection at any time following PIT. Routine posttransplant testing of PIT recipients demonstrated that neither CMV transmission nor CMV infection occurred after PIT.
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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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correction of insulin sensitivity and glucose disposal after Pancreatic Islet Transplantation preliminary results
Diabetes Obesity and Metabolism, 2010Co-Authors: D Hirsch, Camillo Ricordi, Rodolfo Alejandro, Jon S Odorico, N A Radke, Matthew S Hanson, Juan S Danobeitia, Debra A Hullett, Luis A FernandezAbstract:Aims: Pancreatic Islet Transplantation (PIT) represents a potential curative treatment for patients with type 1 diabetes, but only 10-15% of patients remain insulin independent 5 years post-transplant. It is not known whether intrinsic insulin resistance exacerbated by immunosuppression plays a pivotal role in low graft survival. The study objective was to understand the changes in insulin resistance, glucose effectiveness (S g ) and free fatty acid dynamics (FFAd) before and after PIT. Methods: Insulin sensitivity index (S i ), Sg and FFAd were measured before and after PIT in 10 lean patients, 8 of whom reached insulin independence. Modified Bergman minimal model of frequently sampled intravenous glucose tolerance tests were performed pretransplant and at 12 months post-transplant. Nine non-diabetic control (NDC) subjects matched by age, gender and BMI were used. Results: Pretransplant S i and S g were 3.5 ± 0.8 x 10 -5 /min/(pmol/l) and 0.74 ± 0.24 x 10 -2 /min, respectively. S i was significantly lower than matched NDCs [10.8 ± 0.6 x 10 -5 /min/(pmol/l), p < 0.004]; S g did not reach statistical significance (1.27 ± 0.22 x 10 -2 /min, p = 0.25). Compared to pretransplant values, mean post-transplant S i and S g were 9.6 ± 1.3 x 10 -5 /min/(pmol/l) and 1.28 ± 0.22 × 10 -2 /min, respectively, indicating significant improvement for S i but not S g (p = 0.008 and p = 0.06). Twelve-month post-PIT compared to NDC values were not significantly different (p = 0.58 and 0.97, respectively). In addition, fractional disposal rate for FFA which directly depends on the endogenous insulin release (10-20 min) nearly normalized after PIT (p = 0.06). Conclusion: These preliminary findings demonstrate that PIT can restore glucose disposal and insulin sensitivity and partially correct glucose effectiveness and FFAd.
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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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Pancreatic Islet Transplantation for treating diabetes
Expert Opinion on Biological Therapy, 2006Co-Authors: Shinichi Matsumoto, Hirofumi Noguchi, Yukihide Yonekawa, Teru Okitsu, Yasuhiro Iwanaga, Hideo Nagata, Naoya Kobayashi, 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.
John A. Goss - One of the best experts on this subject based on the ideXlab platform.
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Lack of cytomegalovirus transmission after Pancreatic Islet Transplantation.
Cell Transplantation, 2020Co-Authors: Neal R. Barshes, Camillo Ricordi, F. Charles Brunicardi, Amy Mote, A. Paige Schock, Rodolfo Alejandro, John A. GossAbstract:In spite of antiviral prophylaxis, the transmission rate of cytomegalovirus (CMV) after solid organ Transplantation remains high. In contrast, CMV transmission has never been reported following Pancreatic Islet Transplantation (PIT). Eleven (seven CMV seronegative, four CMV seropositive) recipients underwent a total of 26 PITs. Following PIT recipients were monitored clinically and tested monthly for CMV antigenemia. Valganciclovir was given to all patients for 100 days after each PIT. Follow-up ranged from 6 to 24 months (median 14.5 months). Pancreatic Islet grafts were procured from 18 CMV seropositive and 8 seronegative donors (69% and 31% of donors, respectively). In total there were 6 R+D+, 3 R+D-, 12 R-D+, and 5 R-D-PITs. No patient developed CMV antigenemia or symptoms consistent with CMV infection at any time following PIT. Routine posttransplant testing of PIT recipients demonstrated that neither CMV transmission nor CMV infection occurred after PIT.
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health related quality of life after Pancreatic Islet Transplantation a longitudinal study
Transplantation, 2005Co-Authors: Neal R. Barshes, Amy Mote, Rajesh Balkrishnan, Paige A Schock, Charles F Brunicardi, Jason M Vanatta, John A. GossAbstract:Background. Pancreatic Islet Transplantation (PIT) has proven effective in achieving insulin independence, but to date, the impact of PIT on health-related quality of life (HRQL) has not been studied. Methods. Ten patients who have undergone PIT at our institution were administered three HRQL questionnaires: the Hypoglycemia Fear Survey, the 36-Item Short Form Health Survey (SF-36), and a fatigue questionnaire. HRQL was assessed before PIT, then 3, 6, and 12 months after PIT. Responses were compared by analysis of variance and paired Student’s t tests. Results. Hypoglycemia Fear Survey responses demonstrated that hypoglycemia-related anxiety and hypoglycemia-related behavior modification occurred less frequently after PIT (P=0.003 and 0.0001, respectively). The total scores of the hypoglycemia questionnaire were also significantly improved after PIT, from a median score of 156 points before Transplantation to 55 points 3 months after PIT (P=0.004), 38 points 6 months after PIT (P=0.001), and 69 points 12 months after PIT (P=0.04). The median scores of all SF-36 components also improved after PIT. No significant changes were seen in the fatigue symptoms as assessed by the fatigue questionnaire. Conclusion. PIT recipients have less anxiety about the symptoms and consequences of hypoglycemia. PIT recipients also indicate that their behavior requires significantly less modification to prevent or treat hypoglycemia after PIT compared with before PIT. Further investigation is needed to determine whether PIT improves generic measures of HRQL.
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the effect of Pancreatic Islet Transplantation on progression of diabetic retinopathy and neuropathy
Transplantation Proceedings, 2005Co-Authors: Neal R. Barshes, Camillo Ricordi, Amy Mote, Rodolfo Alejandro, Liz Nguyen, Christine A Omahony, F C Brunicardi, A P Schock, John A. GossAbstract:Abstract Introduction Pancreatic Islet Transplantation (PIT) has only become an effective treatment for type 1 diabetes mellitus within the past 4 years. As a result, the long-term effects of PIT on progression of diabetic neuropathy and retinopathy are unknown. The benefit of halting or improving diabetic neuropathy and retinopathy is of particular interest since most PIT recipients have not developed the advanced complications of diabetes. Herein, we describe the improvement and stabilization of diabetic neuropathy and retinopathy in 12 PIT recipients. Patients and methods Between January 1, 2002, and June 30, 2004, there have been 12 patients who have received PIT. Currently, there are eight patients who have sufficient follow-up to assess the progression of diabetic retinopathy and neuropathy. To assess for disease progression, patients were examined by a single ophthalmologist and single neurologist throughout the study period. Eye exams were performed using a slit-lamp exam while neurological status was assessed using electromyelograms and clinical exams. Results All PIT recipients had decreases in hemoglobin A 1 C and increases in serum C-peptide. All study patients had stabilization of their retinopathic disease. One patient demonstrated improvement of retinopathy at 1 year posttransplant. Fifty percent of patients demonstrated improvement or stabilization of their diabetic neuropathy. One patient had mild reinnervation of the fingers and wrist extensors by clinical exam 1 year posttransplant. Four patients exhibited an average decrease of 19% in sural nerve conduction velocities. Conclusion Our series has demonstrated that all PIT recipients have had stabilization of their diabetic retinopathy and that 50% of patients exhibited stabilization or even improvement of their diabetic neuropathy.
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inflammation mediated dysfunction and apoptosis in Pancreatic Islet Transplantation implications for intrahepatic grafts
Journal of Leukocyte Biology, 2005Co-Authors: Neal R. Barshes, Samuel Wyllie, John A. GossAbstract:Recent advances in clinical protocols have improved the outcomes of Pancreatic Islet Transplantation (PIT), yet PIT recipients typically require Pancreatic Islet grafts derived from multi- ple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of Pancreatic Islet tissue undergoes apoptosis within the first several days post-Transplantation, strongly suggest the involve- ment of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1 appears to be among the most important inflammatory mediators, causing pan- creatic Islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) syn- thase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the Pancreatic Islets, and depletion or inhibition of Kupffer cells improves outcomes following exper- imental PIT. Immediately after Transplantation, the Pancreatic Islets are perfused only by portal vein blood until the process of angiogenesis re- stores arterial blood flow some 7-10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion mole- cules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the imme- diate post-transplant period, hepatocytes may con- tribute to Pancreatic Islet injury through the pro- duction of NO. This paper reviews literature re- garding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the patho- physiology of hepatic ischemia-reperfusion and their relation to the survival and function of intra- hepatic Pancreatic Islet grafts. J. Leukoc. Biol. 77: 000-000; 2005.
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transaminitis after Pancreatic Islet Transplantation
Journal of The American College of Surgeons, 2005Co-Authors: Neal R. Barshes, Camillo Ricordi, Amy Mote, Rodolfo Alejandro, Sarah E Goodpastor, Rajesh Balkrishnan, Paige A Schock, Charles F Brunicardi, John A. GossAbstract:Background An asymptomatic, self-limited transaminitis uniformly follows Pancreatic Islet Transplantation (PIT) performed through portal vein (PV) infusion. The underlying cause and significance of this transaminitis is unclear. Study design Records of all patients with insulin-dependent diabetes mellitus who had undergone PIT at our institution were reviewed. All PITs were performed in conjunction with a remote Pancreatic Islet isolation center and done through percutaneous transhepatic PV infusion. Alanine aminotransferase (ALT) levels, serum glucose concentrations, insulin requirements, and color-flow Doppler ultrasonography examinations of the right upper quadrant were assessed before and after PIT. Results Eleven patients have undergone a total of 26 PITs. An elevated ALT level occurred in all 11 patients (100%) after the first PIT, with the median post-PIT peak ALT level reaching 187 IU/L. Transaminitis was less frequent and less marked after the second PIT. A negative correlation between viability of the Pancreatic Islets transplanted (r = −0.44, p = 0.03) and a positive correlation between the ratio of maximum to initial PV pressure (r = 0.41, p = 0.04) were seen with the subsequent ALT peak. Color-flow Doppler ultrasonography examinations showed no occurrences of PV thrombosis or intrahepatic hematoma. Finally, the degree of transaminitis did not correlate with post-PIT insulin requirements, indicating that post-PIT transaminitis cannot be used to measure allograft rejection or function. Conclusions Transaminitis after PIT is common and self-limited. Post-PIT transaminitis does not signal acute rejection or serious procedure-related complications such as PV thrombosis or intrahepatic hematoma.
A James M Shapiro - 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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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.
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Pancreatic Islet Transplantation in the treatment of diabetes mellitus
Best Practice & Research Clinical Endocrinology & Metabolism, 2001Co-Authors: A James M Shapiro, Edmond A Ryan, Jonathan R T LakeyAbstract:Abstract This chapter reviews current developments and future directions in clinical Islet Transplantation. With the recent introduction of glucocorticoid-free immunosuppressive therapies and improved methods for Islet isolation, the success of the procedure has increased substantially. Challenges ahead include progress with international multicentre trials, development of single donor protocols, progress in clinical tolerance based therapies to lower overall risk of immunosuppression, and ultimately finding an alternative source to provide effective therapy for more patients with diabetes. Recent advances in stem cell biology and xenoTransplantation may soon provide this opportunity.
Xin Xiao Zheng - One of the best experts on this subject based on the ideXlab platform.
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biopatterned ctla4 fc matrices facilitate local immunomodulation engraftment and glucose homeostasis after Pancreatic Islet Transplantation
Diabetes, 2016Co-Authors: Wensheng Zhang, Vijay S Gorantla, Phil G Campbell, Yang Li, Yang Yang, Chiaki Komatsu, Lee E Weiss, Xin Xiao ZhengAbstract:Pancreatic Islet Transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor Islets and the need for long-term multidrug immunosuppression to prevent alloimmune Islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains Islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and cotransplanted with allogeneic Islets under the renal capsule to create an immunoregulatory microenvironment around the Islet allograft. We achieved long-term engraftment of small loads of allogeneic Islet cells with 40% of MHC-mismatched mouse recipients maintaining sustained normoglycemia following Pancreatic β-cell ablation by streptozotocin. Biopatterned CTLA4/Fc local therapy was associated with expansion of Foxp3 + regulatory T cells and shifts in cytokine production and gene expression from proinflammatory to regulatory profiles, thus substantially benefiting Islet allografts survival and function. This study is a new paradigm for targeted therapies in PIT that demonstrates the favorable effects of immune alterations in the transplant milieu and suggests a unique strategy for minimizing systemic immunosuppression and promoting Islet allograft survival.
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Biopatterned CTLA4/Fc Matrices Facilitate Local Immunomodulation, Engraftment, and Glucose Homeostasis After Pancreatic Islet Transplantation
Diabetes, 2016Co-Authors: Wensheng Zhang, Vijay S Gorantla, Phil G Campbell, Yang Li, Yang Yang, Chiaki Komatsu, Lee E Weiss, Xin Xiao Zheng, Mario G. SolariAbstract:Pancreatic Islet Transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor Islets and the need for long-term multidrug immunosuppression to prevent alloimmune Islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains Islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and cotransplanted with allogeneic Islets under the renal capsule to create an immunoregulatory microenvironment around the Islet allograft. We achieved long-term engraftment of small loads of allogeneic Islet cells with 40% of MHC-mismatched mouse recipients maintaining sustained normoglycemia following Pancreatic β-cell ablation by streptozotocin. Biopatterned CTLA4/Fc local therapy was associated with expansion of Foxp3 + regulatory T cells and shifts in cytokine production and gene expression from proinflammatory to regulatory profiles, thus substantially benefiting Islet allografts survival and function. This study is a new paradigm for targeted therapies in PIT that demonstrates the favorable effects of immune alterations in the transplant milieu and suggests a unique strategy for minimizing systemic immunosuppression and promoting Islet allograft survival.
Phil G Campbell - One of the best experts on this subject based on the ideXlab platform.
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biopatterned ctla4 fc matrices facilitate local immunomodulation engraftment and glucose homeostasis after Pancreatic Islet Transplantation
Diabetes, 2016Co-Authors: Wensheng Zhang, Vijay S Gorantla, Phil G Campbell, Yang Li, Yang Yang, Chiaki Komatsu, Lee E Weiss, Xin Xiao ZhengAbstract:Pancreatic Islet Transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor Islets and the need for long-term multidrug immunosuppression to prevent alloimmune Islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains Islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and cotransplanted with allogeneic Islets under the renal capsule to create an immunoregulatory microenvironment around the Islet allograft. We achieved long-term engraftment of small loads of allogeneic Islet cells with 40% of MHC-mismatched mouse recipients maintaining sustained normoglycemia following Pancreatic β-cell ablation by streptozotocin. Biopatterned CTLA4/Fc local therapy was associated with expansion of Foxp3 + regulatory T cells and shifts in cytokine production and gene expression from proinflammatory to regulatory profiles, thus substantially benefiting Islet allografts survival and function. This study is a new paradigm for targeted therapies in PIT that demonstrates the favorable effects of immune alterations in the transplant milieu and suggests a unique strategy for minimizing systemic immunosuppression and promoting Islet allograft survival.
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Biopatterned CTLA4/Fc Matrices Facilitate Local Immunomodulation, Engraftment, and Glucose Homeostasis After Pancreatic Islet Transplantation
Diabetes, 2016Co-Authors: Wensheng Zhang, Vijay S Gorantla, Phil G Campbell, Yang Li, Yang Yang, Chiaki Komatsu, Lee E Weiss, Xin Xiao Zheng, Mario G. SolariAbstract:Pancreatic Islet Transplantation (PIT) represents a potential therapy to circumvent the need for exogenous insulin in type 1 diabetes. However, PIT remains limited by lack of donor Islets and the need for long-term multidrug immunosuppression to prevent alloimmune Islet rejection. Our goal was to evaluate a local immunoregulatory strategy that sustains Islet allograft survival and restores glucose homeostasis in the absence of systemic immunosuppression. Nanogram quantities of murine CTLA4/Fc fusion protein were controllably delivered within human acellular dermal matrix scaffolds using an inkjet-based biopatterning technology and cotransplanted with allogeneic Islets under the renal capsule to create an immunoregulatory microenvironment around the Islet allograft. We achieved long-term engraftment of small loads of allogeneic Islet cells with 40% of MHC-mismatched mouse recipients maintaining sustained normoglycemia following Pancreatic β-cell ablation by streptozotocin. Biopatterned CTLA4/Fc local therapy was associated with expansion of Foxp3 + regulatory T cells and shifts in cytokine production and gene expression from proinflammatory to regulatory profiles, thus substantially benefiting Islet allografts survival and function. This study is a new paradigm for targeted therapies in PIT that demonstrates the favorable effects of immune alterations in the transplant milieu and suggests a unique strategy for minimizing systemic immunosuppression and promoting Islet allograft survival.
