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The alginate‐poly‐L‐lysine‐alginate membrane: Evidence of a protective effect on microencapsulated islets of Langerhans following exposure to cytokines
Author(s) -
Tai Isabella T.,
Vacek Ivan,
Sun Anthony M.
Publication year - 1995
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.1995.tb00064.x
Subject(s) - islet , pancreatic islets , nod mice , proinflammatory cytokine , endocrinology , tumor necrosis factor alpha , medicine , streptozotocin , insulin , insulitis , interleukin , chemistry , diabetes mellitus , biology , cytokine , inflammation
In past experiments, we demonstrated that allografts and xenografts of pancreatic islets encapsulated in alginate‐polylysine‐alginate (APA) microcapsules were protected from immunorejection and that in both streptozotocin‐induced and spontaneously diabetic animals diabetes was reversed for extended periods of time. Because of growing evidence that cytokines may play an important role in graft rejection, it is important to determine whether the APA capsular membrane can also provide a protective barrier against cytotoxic actions of cytokines. In this study, free and encapsulated rat islets were exposed in vitro to interleukin 1, 2, and 6 (IL‐1, IL‐2, and IL‐6) to tumor necrosis factor (TNF) and interferon (INT), then challenged with 20 mM glucose for 24 hr to evaluate physiological response in terms of insulin secretion. Although IL‐2 and 6 were found to have no effect on the pancreatic islets (free or encapsulated), IL‐1, TNF, and INT were shown to interfere with the physiological pattern of insulin secretion from the free islets; microencapsulated islets' function was not affected. Transmission electron microscopy (TEM) of the rat islets exposed to the five types of cytokines revealed that IL‐1, TNF, and INF exerted morphological changes to the free islets while encapsulated islets were not affected. No changes were detected in free or encapsulated islets exposed to IL‐6 or IL‐2. In addition, encapsulated islets were transplanted into normal BALB‐c mice and into spontaneously diabetic NOD mice for 3 to 5 months and then recovered. The recovered islets were shown to continue to respond to glucose challenge in a physiological manner. The results of this study showed that, although exposure of some cytokines to free islets results in changes in the normal physiological response of the islets to glucose challenge as well as in ultrastructural changes within the cells, microencapsulated islets were not impaired by the exposure to the same cytokines.