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At least 19 recordsLinked to original sources
PubMed1995

[Islet of Langerhans transplantation].

Islet of Langerhans transplantation is considered to be the ideal treatment for type I insulin-dependent diabetes. The permanent and adapted insulin secretion obtained by this method ensures prevention or even regression of the degenerative lesions which now constitute the severity of this frequent disease. Islets of Langerhans can be isolated from human pancreas and implanted freely in the liver or spleen. However, this source of grafts is limited and implantation of alloantigens requires the use of anti-rejection immunosuppressant therapy. The isolation of islets of Langerhans from porcine pancreas would represent an ideal solution to the shortage of human grafts, but the high immunoreactivity of xenoantigens prevents the possibility of free graft. For this reason, cell encapsulation systems in semipermeable and biocompatible membranes, at least theoretically able to ensure permanent tolerance of the cells, have been developed. The objective of this review is to inform general surgeons about the state of progress of studies in an area considered to be the first step of a promising therapeutic era in which they will be required to participate: that of cell therapy.

Humans↗
PubMed2001

[Focus on Islets of Langerhans transplantation].

INDICATIONS: There are two types of indications for Langerhans islets transplantation, patients with type 1 diabetes mellitus who have a functional kidney graft but who cannot be candidates for total pancreas transplantation, and soon, patients without renal failure who develop particularly uncontrollable diabetes mellitus. SEVERAL BASIC CONDITIONS: Several conditions are required for the success of Langerhans islet transplantation: a laboratory with demonstrated skill is isolating islets, a sufficiently large number of islets for injection (600,000 for a 60-kg patient), fresh islets harvested within less than 24 hours before transplantation, effective immunosuppressive treatment with no toxic effect on Langerhans islets. The injection is a simple procedure performed under local anesthesia via transhepatic catheterization of the portal vein. RESULTS: Through 2000, 10% to 20% of implanted grafts were functional at 1 year. Islets survival has exceeded 80% at 1 year. The gold standard for success is withdrawal of insulin therapy and normal glucose control. Islets grafts will undoubtedly become the next important step in the treatment of type 1 diabetes mellitus, but other techniques are also envisaged for the future.

Age Factors↗
PubMedDate not supplied

Gene combination transfer to block autoimmune damage in transplanted islets of Langerhans.

Islet transplantation therapy would be applicable to a wider range of diabetic patients if donor islet acceptance and protection were possible without systemic immunosuppression of the recipient. To this aim, gene transfer to isolated donor islets ex vivo is one method that has shown promise. This study examines the combined effect of selected immunomodulatory and anti-inflammatory genes known to extend the functional viability of pancreatic islet grafts in an autoimmune system. These genes, indoleamine 2,3-dioxygenase (IDO), manganese superoxide dismutase (MnSOD), and interleukin (IL)-1 receptor antagonist protein (IRAP), were transferred to isolated NOD donor islets ex vivo then transplanted to NODscid recipients and evaluated in vivo after diabetogenic T-cell challenge. The length of time the recipient remained euglycemic was used to measure the ability of the transgenes to protect the graft from autoimmune destruction. Although the results of these cotransfections gave little evidence of a synergistic relationship, they were useful to show that gene combinations can be used to more efficiently protect islet grafts from diabetogenic T cells.

Adenoviridae↗
PubMedDate not supplied

[A comparative study of pancreatic-duodenal transplantation, islets of Langerhans transplantation, and insulin treatment, in the control of experimental diabetes in the rat].

Sixty outbred Wistar rats were randomly assigned to five experimental groups: GI-10 non-diabetic control rats; GII-10 untreated diabetic control rats; GIII-10 diabetic rats treated with retard porcine insulin; GIV-20 diabetic rats that received pancreaticoduodenal transplantation (PDT) from normal donor rats; GV-10 diabetic rats submitted to islet of Langerhans transplantation (ILT) into the portal vein. The animals were housed in metabolic cages for six periods of 24 hours during 30 days and body weight, water and food intake, urine output, blood and urinary glucose were recorded. Diabetes was induced by I.V. administration of Alloxan (42 mg/kg of body weight); PDT was performed by microsurgical techniques and islets were prepared without enzymes. To prevent rejection. Cyclosporin A (10 mg/kg of body weight) was utilized in transplanted rats. PDT consistently and significantly (p < 0.05) improved the metabolic abnormalities of the diabetic rats, by restoring the body weight gain, and immediate relief of polydipsia, polyphagia, polyuria, hyperglycemia and glucosuria observed in pre-treatment period. PDT was more effective than ILT and this over insulin therapy on control of the diabetic state. However, the observed complications in GIV and GV, due to surgery and immunosuppression, should be analysed for the real benefits of the alternative therapy can be superior to eventual fails to the conventional therapy with insulin.

Animals↗
PubMed1989

Angiogenesis and hemodynamics of microvasculature of transplanted islets of Langerhans.

Transplantation of isolated islets of Langerhans is frequently followed by early loss of islet function. Because whether this is caused by insufficient vascularization or graft rejection is unknown, angiogenesis and microvascularization of islet grafts were studied in vivo by means of intravital microscopy. After transplantation of syngeneic islets in hamster dorsal skin-fold chambers, 97% (n = 66) of the islets exhibited the first signs of angiogenesis at days 2-4, characterized by sinusoidal sacculations and capillary sprouts. After 10 days, angiogenesis was completed, consisting of a microvascular network similar to those of islets in situ: arterial supply, afferent and efferent capillary loops, and venular drainage. Functional density of microvessels was 700.1 +/- 127.0 cm-1, and erythrocyte velocity was 0.58 +/- 0.35 mm/s. Intracellular insulin was demonstrated immunohistochemically. Electron-microscopic studies revealed normal fine structure of the capillary wall. The model allows in vivo analysis of microvascular phenomena occurring in host-vs.-graft reaction after allogeneic and xenogeneic islet transplantation. Furthermore, it may be used to quantitatively assess immunosuppressive regimens.

Animals↗
PubMed1993

[Islet of Langerhans transplantation in humans].

Islet of Langerhans transplantation is an alternative to whole pancreas transplantation for type I diabetic patients, in whom exogenous insulin therapy has not prevented the occurrence of systemic complications. Thanks to a new isolation technique of human islets, 45 patients have been transplanted worldwide since 1988, of whom only 7 have become totally insulin-independent. Rejection and quality of the islet preparations are problems which remain to be solved. Autotransplantation of islets has been proposed in patients undergoing a pancreatectomy for benign disease. The present report concerns two of our patients who had a pancreatectomy with islet autotransplantation. Both patients are insulin-independent 3 and 11 months postoperatively, with satisfactory metabolic tests. Islet autotransplantation can be proposed when pancreatectomy for non-malignant disease is performed. This method may prevent the development of insulin-dependent diabetes, known to be particularly labile. Because of the sophisticated technical procedures required, human islet isolation is at present only performed in a small number of medical centers and still is in the field of medical experimentation.

Adult↗
PubMed1990

A novel technique for studies on the microvasculature of transplanted islets of Langerhans in vivo.

Transplantation of isolated islets of Langerhans in diabetic patients is frequently followed by an early loss of function due to acute rejection. Since the primary target of host-vs-graft reaction is the endothelium of the microvessels, it is of great importance to analyze the microcirculation of freely grafted pancreatic islets. For this purpose we present a new model, allowing for intravital microscopy of the microvasculature of transplanted islets of Langerhans. The islets are isolated from Syrian golden hamsters and DA-rats, respectively, by a modified collagenase digestion technique. Subsequently, the islets are transplanted into a hamster dorsal skinfold chamber. Using intravital fluorescence microscopy and video techniques, the microcirculation of the islet grafts can be observed repeatedly over a time period of up to four weeks. Quantitative analysis of the microhemodynamics, i.e. functional capillary density, capillary RBC-velocity and microvascular diameters, can be performed by means of a computer assisted image analysis system. In addition, the model allows for investigation of the flow behaviour of white blood cells and their interaction with the endothelium of the microvascular segments. For the first time a model is presented, enabling for in vivo analysis of the revascularization process and microcirculatory function of transplanted islets of Langerhans. Furthermore, the model allows to assess microvascular phenomena during host-vs-graft reaction as well as effects of immunosuppressive regimens.

Animals↗
PubMed2002

Isolation, transplantation, and functional studies of adult porcine islets of Langerhans.

Transplantation of islets of Langerhans is a possible treatment for type-I diabetes mellitus. However, there is a shortage of donors for such transplantations and the pig may be an alternative source of donor organs. The aims of the study reported here were to establish a method for adult porcine islet isolation that was based on enzymatic digestion using Liberase PI in a semiautomatic set-up, and to evaluate the in vitro and in vivo function of isolated islets. After overnight culture, isolated islets, from five of seven batches, had poor insulin response to an in vitro glucose challenge that was only partially increased by additional challenge with arginine. More than 50% of DNA and 90% of the insulin content was lost during a one-week culture period. With some batch-to-batch variation, in 15 of 25 cases, 4,000 to 7,000 porcine islets cured streptozotocin diabetic nude mice within three weeks following transplantation. 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.

Animals↗
PubMed1975

Transplantation of islets of Langerhans.

Transplantation of insulin-secreting tissues is currently being evaluated as a possible method of treating diabetic patients. Isolation of islets of Langerhans from the rat pancreas is now routinely accomplished, and methods for islet isolation from the human pancreas are being explored. Transplantation of isolated islets into isologous rats is capable of reversing streptozotocin-induced diabetes. Unfortunately, isolated islets are not immunologically privileged and various immunosuppression regimens have not effectively obviated the rejection phenomena seen in rat allograft experiments.

Animals↗
PubMedDate not supplied

[Islet of Langerhans transplantation. A comparative study of two different methods for isolating islet cells from rat pancreas].

Two different methods for isolation of islet of Langerhans on control of metabolic abnormalities of alloxan-induced diabetic rat were tested. Sixty rats were randomly assigned to four experimental groups: GI included 10 non-diabetic control rats, GII included 10 diabetic control rats, without treatment, GIII included 20 diabetic rats (10 inbred and 10 outbred rats) that received islet of Langerhans transplantation (ILT) using islet cells prepared by collagenase, and GIV included 20 diabetic rats (10 inbred and 10 outbred rats) submitted to ILT using islet cells prepared by nonenzymatic method. Clinical and laboratory parameters at beginning and 4, 7, 14, 21 and 30 days of follow-up were recorded. Outbred rats were immunosuppressed with cyclosporin A, diabetes was induced by e.v. alloxan administration, and islet cells were isolated from normal donor Lewis rats and injected into the portal vein. ILT corrected the body weight gain, polyuria, polydipsia, polyphagia, and the high levels of blood and urine glucose in 73.7% of rats treated by enzymatic method and in 64.7% of those ones treated by nonenzymatic method. However, there was no significantly difference between the two methods (P > 0.50). We did not also observe significantly difference between the two methods when ILT was performed either in inbred or outbred rats. We concluded that ILT performed by nonenzymatic method may be an alternative treatment for diabetes due to be less expensive and to have possible advantages in the isolation process.

Animals↗
PubMed1977

[The immunofluorescence-microscopical evidence of insulin and glucagon in transplantated isolated Langerhans' islets in diabetic rats and dogs (author's transl)].

With the histochemical immunofluorescence technique were demonstrated the insulin and glucagon in the transplantated isolated Langerhans' islets in the liver at diabetic rats and dogs. Further on were tested the diabetic metabolic level with aid of clinico-chemical methods during the period of investigation (blood glucose, serum insulin, glucose tolerance test). It was found that after transplantation, 1 year by the rats and more than 8 weeks by the dogs, is existing a normoglycemic level. In the transplanted islets were seen a good immunofluorescence of insulin in the B cells and the glucagon in the A cells in all investigated stages.

Animals↗
PubMed2003

Islet of Langerhans transplantation for the treatment of type 1 diabetes.

Islet of Langerhans transplantation is gaining recognition as a therapy for type 1 diabetes. The procedure involves enzymatic digestion of the pancreatic tissue, purification of the islets from the exocrine tissue, infusion of the islets into the portal vein and implantation in the liver. Until 1999, and overall rate of insulin independence of 14% at one year was reported in the International Islet Transplant Registry. The results of the "Edmonton protocol" since 2000 were a breakthrough in the field, with reports of 80% insulin independence at 1-year after solitary islet transplantation in non uremic patients with brittle type 1 diabetes. A rapamycin-based, steroid-free, islet-sparing immunosuppressive regimen was designed and the problem of the insufficient islet mass was tackled by sequential infusions of islets isolated from at least two pancreatic. The University of Geneva has been involved in clinical islet transplantation since 1992, and has performed 51 allogeneic and 17 autologous. Twenty-one patients have been transplanted in Geneva since 2002. They were five solitary islet transplants, 14 islet after kidney transplants and two simultaneous islet-kidney (SIK) recipients. Insulin independence was achieved in 67%.

Diabetes Mellitus, Type 1↗
PubMed1990

Experiments on a new hollow fiber membrane for immuno isolated transplantation of islets of Langerhans.

Immunoisolated transplantation of xenogeneic islets could solve problems concerning the immunology of islet transplantation. This study presents results from in vitro and in vivo experiments in rodents by the use of a PEEK-hollow fiber. Glucagon secretion of encapsulated islets during a 48-hour-culture period sustained on the same level from day 2 to 28. There were no significant differences in glucose (16.7 mmol/l)-stimulated insulin release after 6, 14 or 28 days in culture. Contrary, intraperitoneal transplantation of 800 encapsulated islets resulted in a normoglycemia of 3.8 days (medium survival time) which was similar to that of not encapsulated controls. It was concluded that a more open ultrastructure of the membrane tested could result in a minimization of the diffusion distance and overcome principle geometric problems of the hollow fiber model.

Animals↗
PubMed1993

[Immunologic isolation of transplanted islets of Langerhans: microcapsules with defined molecular limits].

Immunoisolated transplantation of islets of Langerhans in barium alginate microcapsules is a promising therapeutic approach to cure diabetes. An improved membrane for the coating of barium alginate microcapsules has been developed. Chemically stable barium alginate microcapsules with a controlled molecular weight cutoff between 9400 and 40,500 D were obtained after coating of barium alginate capsules in Polybrene solutions. Microcapsules prepared by this new method were still freely permeable to low molecular weight substances.

Alginates↗
PubMed1977

[Histological and immunohistochemical investigations on the transplanted isolated islets of Langerhans in diabetic rats (author's transl)].

Isologous isolated islets of LANGERHANS were transplanted in the peritoneum and through the portal vein in the liver of diabetic rats. With the help of histological and immunohistochemical investigations, estimation of blood sugar and glucose tolerance tests was tested over a period of 12 month, whether the peritoneum or the liver is more suited as transplantation site for isolated islets of LANGERHANS. After transplantation of islets of LANGERHANS in the peritoneum of diabetic rats the blood glucose decreased and this effect could be maintained over a period of three months. The histological investigations showed strong periinsulinar reactions and the immunohistochemical insulin and glucagon proofs prospered over a period of three months. After transplantation of isolated islets in the liver it resulted in a normalization of blood glucose levels up to 12 months after transplantation and in this time prospered the immunohistochemical insulin and glucagon proof. These results have suggested, that the liver is more suited as transplantation site for isolated islets of LANGERHANS than the peritoneum.

Animals↗
PubMedDate not supplied

Reinnervation of isolated islets of Langerhans transplanted beneath the kidney capsule in the rat.

Neural regulation of islets of Langerhans mediates responses to stress and food ingestion. Transplantation of isolated islets offers hope to patients with insulin dependent diabetes mellitus but denervation of isolated islets may affect the capacity for appropriate metabolic control. Previous examination of the endocrine response to stress in islet autografted dogs revealed differences consistent with loss of neural regulation. Therefore, in the present study, islets grafted in rats were examined for extent and nature of reinnervation. Islets isolated from syngeneic donors were grafted under the kidney capsule of Wistar-Furth rats (n = 7) after 3 wk of streptozotocin induced diabetes. After 4 mo, graft-bearing kidneys were recovered and processed for double immunofluorescence. Antibodies were directed against (a) neuron associated proteins: synapsin (SYN) and L1; (b) neurotransmitters; tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP); and (c) islet hormones: insulin and somatostatin. SYN and L1 immunoreactivities in nerve fibres suggested reinnervation of the grafted islets although fibres were not associated with structures within the transplanted islets as in intact islets. CGRP immunoreactivity was observed in fibres and in a subpopulation of cells within intact islets but only in cells of the grafted islets. VIP, TH, and NPY immunoreactivities were found in nerve fibres of intact islets but only VIP was observed in fibres of grafted islets suggesting an absence of sympathetic reinnervation. In conclusion, transplanted islets of Langerhans become reinnervated but with a distribution and complement of neurotransmitters distinct from intact islets.

Animals↗