islets of langerhans transplantation

..Registry data on patients with type 1 diabetes mellitus who undergo pancreatic islet transplantation indicate that only 8 percent are free of the need for insulin therapy at one year...

..When injected into diabetic mice, the insulin-producing cells undergo rapid vascularization and maintain a clustered, islet-like organization...

..Therefore, the objective of the present study was to develop a technique for imaging survival of transplanted islets in the peritransplant and early posttransplant phase...

..However, for islet transplants to become a widespread clinical reality, diabetes reversal must be achieved with a single donor to reduce risks and costs and increase the availability of transplantation...

..We conducted an international, multicenter trial to explore the feasibility and reproducibility of islet transplantation with the use of a single common protocol (the Edmonton protocol)...

..These findings have provided new insight into the nature of the IBMIR and offer several new strategies to improve the outcome of clinical islet transplantation...

..To avoid systemic treatment, the aim of the present study was to render the islet graft blood biocompatible by applying a continuous heparin coating to the islet surface...

..In the present study, a technique for intramuscular islet transplantation was developed and compared with intraportal islet transplantation in a syngeneic rat model...

..In this study, we investigated the capacity of human mesenchymal stem cells (MSCs) to adhere to human islets of Langerhans and their effects in immune modulation and during blood interactions in vitro...

..Overall, these data demonstrate the beneficial effect of liraglutide on cultured human islets, preserving islet mass. They support the design of clinical studies looking at the effect of liraglutide in clinical islet transplantation...

..This protective effect indicates that thrombin plays a pivotal role in IBMIR and suggests that thrombin inhibition can improve the outcome of clinical islet transplantation...

..The aim of the current study was to evaluate striated muscle as a potential angiogenic site for islet transplantation...

..The technique has potential to be used to assess approaches to enhance islet survival and engraftment in clinical transplantation...

..Here we examined the effect of non-viral VEGF delivery using UTMD on transplanted islets in vivo...

..Human islets transplanted intraportally into the liver become poorly revascularized. This could contribute to the loss of function in human islets transplanted into the liver over time...

..Our results suggest this immunosuppressive protocol may allow long-term graft survival...

..The effect of neutralizing anti-IL-17 and recombinant IL-25 on the development of diabetes in NOD mice, a model of spontaneous autoimmune diabetes, was investigated in this study...

..1 to 5.8 +/- 0.3 after 1 Tx in Group 2). HYPO scores markedly decreased in both groups. Combined treatment of etanercept and exenatide improves islet graft function and facilitates achievement of insulin-independence with less islets...

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..In this study, the authors investigated whether compounds previously shown to affect TF and macrophage chemoattractant protein (MCP)-1 expression in monocytes and endothelial cells have the same effect in human islet cells...

..The aim of the study was to determine whether purified beta cells can replicate in vitro and whether this is enhanced by extracellular matrix (ECM) and growth factors...

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..0 to 3.12 for tacrolimus. Given the potential toxicity of these agents to islets, the findings in this study may have implications for designing the next generation of immunosuppressive protocols for islet transplantation...

..The scaffold may also be useful to deliver bioactive molecules to modify the microenvironment surrounding the transplanted islets and, thus, enhance islet survival and function...

..p. into streptozotocin-induced diabetic mice, restored normoglycemia within 2 weeks. The data presented here demonstrate the feasibility of using ASCs as a source of autologous stem cells to differentiate into the pancreatic lineage...

..In conclusion, tissue factor present in both the islets and the culture medium and elicits IBMIR, which affects the function of the transplanted islets...

..These results provide evidence that Fas/FasL-mediated programmed cell death plays a significant role in the pathogenesis of autoimmune diabetes...

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..Here we investigated whether co-transplantation of neural crest stem cells (NCSCs) with islets improves islet survival and function in normoglycaemic and diabetic mice...

..The present study tested the hypothesis that the angiostatic factor thrombospondin-1 (TSP-1), which is normally present in islets, restricts intra-islet vascular expansion posttransplantation...

..In addition, XIAP has enhanced long-term murine islet allograft survival. The complexities of both intrinsic and extrinsic apoptotic pathway inhibition are discussed in depth...

..For type 1 diabetes, as remission develops, progression from stage 4 to stage 2 is typically found. Delineation of these stages provides insight into the pathophysiology of both progression and remission of diabetes...

..A local multiorgan donor pancreas procurement program can provide a source for optimized isolation of purified viable islets for transplantation into patients with type 1 diabetes mellitus receiving best medical therapy...

..All together, islet cell transplantation is moving forward...

..An elevation of creatinine appears to be a contraindication to this immunosuppressive regimen. For the subjects who had labile type 1 diabetes that was difficult to control, the risk-to-benefit ratio is in favor of islet transplantation...

..We evaluated the effect of exenatide on insulin secretion after islet transplantation...

..Our preliminary results thus suggest that a combination of maximized viable islet yield, pretransplant islet culture, and preemptive immunosuppression can result in successful single-donor islet transplants...

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..Increased apoptosis and reduced beta-cell mass were also found in islets exposed to chronic hyperglycemia, suggesting that sustained hyperglycemia increased apoptosis in transplanted beta-cells...

..The results implicate changes in islet function after intraportal transplantation. Such dysfunction may contribute to the high number of islets needed for successful transplantation in diabetic individuals...

..In conclusion, several inflammatory mediators were expressed in isolated islets, particularly at an early stage after isolation, indicating that a few days of culture could be beneficial for the outcome of islet transplantation...

..The present study investigated and compared relevant gluco-metabolic parameters in pigs, monkeys and the pig-to-monkey islet transplantation model to gain insight into the potential clinical outcome of pig-to-human islet transplantation...

..EP1013 (N-benzyloxycabonyl-Val Asp-fluoromethyl ketone [zVD-FMK]), is a broad-spectrum caspase selective inhibitor with no observed toxicity in rodents...

..These data provide evidence that islets can be labeled with SPIO and imaged using clinically available 1.5- T MRI...

..The outcomes of these initial investigations are predicted to shape the future boundaries of islet transplantation, diabetes, and transplantation...

..The effect of islet cell transplantation (ICT) on renal function in type 1 diabetes is uncertain and some recent studies report a significant decline in estimated glomerular filtration rate (GFR) and worsening of albuminuria...

..01). CONCLUSIONS: The likelihood of glycemic control after IAT is related to both patient characteristics and islet cell mass. Based on these data, more islet cells may be required for insulin independence than previously thought...

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..These results suggest that inhibition of the p38 pathway may become a new therapeutic strategy to improve graft survival in clinical islet transplantation...

..Graft failure is prevented by blocking lipogenesis. The results suggest that strict antilipogenic intervention might improve outcomes after human islet transplantation...

..To limit the costs involved in the logistics and health care of pigs for clinical xenotransplantation, we have studied whether younger, rather than older, pigs that are typically preferred can be used as islet donors...

..This "portal storm" of immunosuppression may be relevant to intrahepatic islet transplantation...

..The long-term viability and function of transplanted encapsulated neonatal porcine islets was examined in a diabetic patient...

..This study, therefore, represents a promising step toward possible clinical application in human medicine...

..To summarize recent studies on the oxygenation of pancreatic islets and its role in islet transplantation...

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..The possible role of IAPP aggregation and amyloid formation in loss of islet transplant function should be taken into consideration and studied further...

..30 +/- 0.11 vs. 0.13 +/- 0.03 mg, p = 0.012). These results indicate posttransplant exendin-4 treatment in the diabetic recipient with a marginal number of fresh islets expands graft beta-cell mass and improves transplantation outcome...

..This beneficial effect might be used both to ameliorate type 2 diabetes and to improve engraftment rates in clinical islet transplantation...

..We examined the effect of human recombinant PRL (rhPRL) supplementation to the culture media to determine its potential use in the context of clinical islet transplantation...

..Together, these data suggest an important role for decreased ARNT and altered gene expression in the impaired islet function of human type 2 diabetes...

..In this study, the authors investigated the potential of LSF in preventing autoimmune diabetes recurrence after islet transplantation...

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..We show that islet regeneration predominately originates from endogenous cells but that introduced spleen cells can also contribute to islet recovery...

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..These results demonstrate that adult BM cells are capable of trans-differentiating into a pancreatic lineage in vitro and may represent a pool of cells for the treatment of diabetes mellitus...

..These studies suggest that PET imaging of lentivirus-transduced islets could provide a safe and feasible method for long-term monitoring of islet graft survival...

..These results contrast with the efficacy of AdCTLA4Ig we observed in a rat islet allotransplantation model and suggest that islet xenograft rejection might be more difficult to control...

..Taken together, our data suggest that RGP islets are comparable in terms of viability and potency to CGP islets. RGP may be of assistance in maximizing the number of islet preparations successfully used in transplant protocols...

..85, P<0.01). QIVIPA appears as a reliable test to monitor islet graft potency, applicable to validate new methods to produce primary islets or other human insulin secreting cells...

..Our observations indicate that we should focus on reduction of macrophage activation and on improving the nutrition of encapsulated islets to prevent islet cell death...

..These data suggest that early islet xenograft failure is more common in spontaneously diabetic NOD mice and could be due to a nonspecific inflammatory reaction locally in the grafts...

..Therefore, islets in scaffolds function and restore diabetic animals to normoglycemic levels, similar to islets transplanted underneath the kidney capsule, suggesting scaffolds can be used to create a site for islet transplantation...

..These data demonstrate that the blockade of CD40 ligand and ICOS signaling induces islet allograft tolerance involving a dominant mechanism associated with intragraft regulatory cells and prevents autoimmune diabetes in NOD mice...

..CONCLUSION: Z-DEVD-FMK prevented apoptosis of isolated human islets and improved its function. FBS (10%) improved the islet yield and insulin secretion more than 0.5% HSA...

..These results establish p8 as a novel molecular mediator of glucose-induced pancreatic beta-cell expansion in vitro and in vivo and support the notion of existing beta-cell replication in the adult organism...

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..The ability to maintain islets in culture for prolonged periods is an important step toward the development of islet tissue repositories and distribution centers...

..05). The study demonstrates that short-time pretreatment with the caspase-3 inhibitor DEVD-CMK reduces the capacity of transplanted porcine islets to restore normoglycemia in diabetic nude mice...

..These results demonstrate the long-term durability of agarose microcapsules against autoimmunity in a syngeneic islet transplantation model in NOD mice...

..CONCLUSIONS: Our results suggest that ''glucose toxicity'' plays a role in the immediate demise of intraportal tilapia islet xenografts...

..A therapy aimed at the selective elimination of autoreactive cells and the reeducation of T cells, when combined with control of glycemia, is thus able to effect an apparent cure of established type 1 diabetes in the NOD mouse...

..The SUIT and EIR indexes are thus considered to be useful values for evaluating islet transplantation, especially for single islet transplantation...

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..Also, we have demonstrated that, in the NOD model, recipient conditioning resulting in as low as 1% of chimerism is sufficient to promote engraftment of the BM donor-specific islets of Langerhans...

..Incorporation of the RGD sequence in the HI loop of the fiber knob allows highly efficient transfection efficiency to nonhuman primate insulin-producing cells and adequate long-term function of the p-cell after transplantation...

..After each islet transplant, she gradually lost insulin independence while maintaining low levels of C-peptide secretion...

..Arterial islet injection, however, does not appear to be a viable islet transplantation technique...

..These studies demonstrate the primary role of MHC class I molecules in causing autoimmune destruction or recurrent diabetes in transplanted islets...

..The effect is likely attributable to its action in preventing effector lymphocyte infiltration into the grafted tissue...

..In conclusion, it is possible to isolate viable islets from adult pigs, using a semiautomatic set-up. With batch-to-batch variation, the islets are able to revert diabetes mellitus when transplanted to diabetic nude mice...

..They only reversed hyperglycemia for less than 3-5 days...

..These results suggest that local modulation of tryptophan catabolism may be a means of facilitating islet transplantation as a therapy for type 1 diabetes...

..The use of inosine should be considered as a potential preventative therapy in humans susceptible to developing Type 1 diabetes and as a possible antirejection therapy for islet transplant recipients...

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..However, this delay in reaching peripheral target organs does not prevent microencapsulated grafts from efficiently clearing glucose after a meal...

..CONCLUSIONS: Well-functioning APIs can be isolated in large numbers. API xenografts can be protected from rejection and can maintain an adequate function for up to 100 days, in rats immunosuppressed with CsA+MMF+LEF...

..These studies indicate that the reestablishment of the cell-matrix interactions by a synthetic matrix in the immediate postisolation period is a useful tool to maintain islet functions in vitro and in vivo...

..Islet expression of IL-4 led to impaired metabolic function in mice receiving a marginal mass of syngeneic islets...

..Studies of the mechanism of glucagon release during hypoglycemia and its disappearance in the absence of beta cells will be conducted in Sprague Dawley rats. ..

..We will also test whether expression of the ligands of LT¿R, LTa¿ or LIGHT, on spleen cells and LT¿R on islet ¿-cells is critical for stimulating ¿-cell regeneration. ..

..Detailed mechanistic studies will be performed and the analyses planned should provide clinically relevant information for rationally developing new tolerance strategies for not only kidney but also all allograft recipients. ..

..These studies are unique and will generate new data on pig-to-NHP XPITx immunobiology and the immune mechanisms influencing development of pig XPITx tolerance. ..

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..This team has worked well together with the aim of curing diabetes through islet transplantation. ..

..In addition, the development of rapid, accurate, and predictive tests of islet viability and function post isolation will contribute to significant improvements in post transplant success. ..

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..This will decrease the number of islets required to achieve normoglycemia in type I diabetic patients. ..

..This will decrease the number of islets required to achieve normoglycemia in type I diabetic patients. ..

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..We anticipate that the use of pre-vascularized islets as part of a composite islet-kidney transplant may provide a new and effective treatment modality for patients with class I diabetes and end-stage renal disease. ..

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..The grafting of islet tissue from a number of different allogeneic strains to spontaneously diabetic BB rats will be used to define and investigate this problem in greater depth...

..Our overall contention is that interruption of T- and B- lymphocyte function during the induction phase represents a novel and potentially powerful means of promoting immunological tolerance to islet allografts. ..

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..The research proposed in this grant will provide significant information to the xenotransplant research and the potential use of porcine islets as an alternative to human tissue for pancreatic islet transplantation. ..

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..This will overcome the requirement for high numbers of islets and the need for intensive immunosuppression. Beneficial results would pave the way for pre-clinical (primates) and clinical applications. ..

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..The commercial goal is to develop an orally active drug which can prevent or delay onset of T1D, and/or improve the transplantation process by reducing the toxicity of immunosuppression and by increasing donor islet yield. ..

..This knowledge offers the potential to use fewer, more effective enzymes in TDE mixtures, leading to increases in the yield and quality of cells recovered from any mammalian organ. ..