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  • 1
    ISSN: 1432-1440
    Keywords: Key words Islet transplantation ; Microencapsulation ; Immunoalteration ; Diabetes ; Alginate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recently, we reported successful transplantation (Tx) of microencapsulated (mc) islets. However, graft failure observed in several cases was associated with an increased foreign body reaction compared to long-term functioning grafts. This study was performed to investigate the impact of an immunoalterating islet pretreatment (12–14 days culture at 22°C) on graft function. After microencapsulation in barium alginate beads the islets were cultured for another day. Diabetic LEWIS rats (blood glucose 〉19 mM) were transplanted with 3500 immunoaltered mc-Wistar islets intraperitoneally. Controls were transplanted with 3500 non-cultured syngeneic or allogeneic mc-islets. Additional syngeneic and allogeneic controls were transplanted with 6000 non-cultured, non-encapsulated islets intraperitoneally. Seventy percent of the recipients of microencapsulated, long-term low temperature cultured islets maintained normoglycemia at least for 15 weeks, while this was true in only 17% of those animals receiving microencapsulated non-pretreated allogeneic islets. Islets in non-encapsulated controls were rejected within several days. Graft function correlated with histologically proven viable islets within the capsules. Microencapsulation of islets markedly prolonged allograft survival compared to non-encapsulated islets; application of an immunoaltering low-temperature culture further improved graft function significantly. These data may support the hypothesis of induction of a reaction against microcapsules by the antigen release from the graft which may be avoided by immunoaltering islet pretreatment.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-5233
    Keywords: Rat Islets ; Transplantation ; Bioartificial Pancreas ; Microencapsulation ; Insulin Secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Immuno-isolated transplantation offers the attractive prospect of being able to transplant xenogeneic islets without immunosuppression. This study introduces a completely new method of coating single islets using a homogenous alginate membrane approximately 10 μm thick. During glucose challenge (perifusion and static incubation) encapsulated islets show the same pattern and quantity of insulin release as non-encapsulated controls. This encapsulation method markedly reduces the amount of transplanted material by reducing the size of the capsule. It is suggested that encapsulated islets may be transplanted into sites such as the renal capsule or omentum or even by intraportal injection into the liver.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-5233
    Keywords: Bioartificial pancreas ; Porcine islets ; Rat islets ; Xenogeneic transplantation ; Alginate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Transplantation of xenogeneic islets in immunoisolating membranes may solve the problems of the availability of human donor organs and long-term immunosuppression. Alginates are widely used for microencapsulation of isolated islets. This study presents data of a new method in which alginate was cross-linked with barium ions. In the perifusion experiment microencapsulated rat islets showed a biphasic insulin release with a short delay of the first phase. During static glucose challenge the insulin release ranged from 40% to 70% compared to free floating controls. In 3 of 11 diabetic mice, transplantation of 800 barium-alginate-bead encapsulated rat islets resulted in a non-fasting normoglycaemia at least up to 70 days. In the same model, transplantation of 3000 encapsulated porcine islets resulted in 6 of 10 recipients in normoglycaemia up to day 70, while 3 animals were still normoglycaemic on day 100. On day 21 after transplantation of encapsulated rat and porcine islets and intraperitoneal glucose tolerance test revealed rapid glucose assimilation in both groups. Histological examination demonstrated well-preserved islets at the end of the experiments. Immunohistological B-cell staining revealed the absence of recruitment of β-cells in the recipient's own pancreas. The barium-alginate microencapsulation method represents a simple one-step method for effective immunoisolated transplantation of large-scale islet preparations.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-5233
    Keywords: Key words Chronic pancreatitis ; Elastase 1 ; Exocrine pancreatic function ; Diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-5233
    Keywords: Alginate ; Islets of Langerhans ; Macroencapsulation ; Microencapsulation ; Transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We have recently demonstrated long-lasting normoglycaemia after transplantation of barium alginate microencapsulated rat and porcine islets. Nevertheless the transplantation results obtained with different microencapsulation techniques have been controversial. Little is known about possible immune interactions between host and encapsulated islet. This study demonstrates in vitro stimulation of lymphoid cells by encapsulated islets that is similar to that of unencapsulated islets. This stimulation was reduced by a 4-day culture with unencapsulated islets only. After macroencapsulation of islets in hollow fibres a stimulatory effect was also observed, but this was less pronounced than after microencapsulation. Empty microcapsules as well as macrocapsules induced lymphoid proliferation as a result of mitogenic impurities in the encapsulation materials themselves. In the same donor-recipient combination in which we have shown successful transplantation, we found activation of the sensibilization arm of the immune system. This suggests that microencapsulation results in protection of the transplanted islets from the action of the effector arm. This lymphoid activation could be triggered by the mitogeniticity of the encapsulation material itself. In the case of alginates these mitogenic factors could not be abolished by culture (i.e. dialysis).
    Type of Medium: Electronic Resource
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