Sammendrag
Abstract
Diabetes treatment by transplantation of encapsulated islets is considered as one of the
future strategies for continuous control of blood glucose levels in diabetic patients. Studies
involving large animal models are an important bridge between feasibility studies in rodents
and clinical trials. This study presents a model for transplantation of encapsulated allogeneic
islets in baboons using a laparoscopic procedure. The polyelectrolyte complex-based
microcapsules composed of sodium alginate, sodium cellulose sulfate and poly(methyleneco-guanidine) was employed. In total ten baboon pancreata were used to harvest islets and
encapsulated islets were then transplanted into two diabetic recipients. The first baboon
received two transplantations of encapsulated islets (total 4,800 IEQ/kg), while the second
baboon received three transplantations (total 29,600 IEQ/kg). Neither baboon achieved
insulin-independence nor euglycemia. However, some islet function was present with
decreased levels of exogenous insulin and positive C-peptide levels recorded. In the first
recipient, clumped microcapsules were observed 14 days after the first transplantation. In
contrast, the second recipient had free-floating microcapsules containing viable islets
detected for up to 55 days (the end of study) after transplantation. Post-transplant histology
and islet viability indicated that this type of microcapsule can prevent allogeneic rejection in
streptozotocin-induced diabetic baboons. The potential of this microcapsule to activate
complement and inflammatory cytokine secretion was evaluated in baboon whole blood.
Both a low complement activation and cytokine secretion indicated a low inflammatory
potential by these microcapsules in baboons.
Keywords: diabetes, allotransplantation of encapsulated islets, large animal model
Chiang Mai, Thailand: IUPAC, 2014, o-16:
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