Xenotransplantation of Pig Islets in Diabetic Dogs with Use of a Microcapsule Composed of Agarose and Polystyrene Sulfonic Acid Mixed Gel.
Kin, Tatsuya *; Iwata, Hiroo +; Aomatsu, Yukio *; Ohyama, Takao *; Kanehiro, Hiromichi *; Hisanaga, Michiyoshi *; Nakajima, Yoshiyuki *
[Article]
Pancreas.
25(1):94-100, July 2002.
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Introduction: The authors have designed a microcapsule composed of agarose and polystyrene sulfonic acid (PSSa) mixed gel that provides a protective barrier against complement attack. Xenografts of islets, encapsulated in an agarose-PSSa microcapsule, have been shown to normalize blood glucose in rodents with chemically induced diabetes for extended periods of time without immunosuppression.
Aim: To investigate the efficacy of agarose-PSSa microencapsulated pig islets in reversing diabetes in a large animal model.
Methodology: Diabetes was induced in beagle recipients by total pancreatectomy. Each recipient received three to five intraperitoneal injections of either encapsulated (n = 5) or nonencapsulated pig islets (n = 2).
Results: In all dogs receiving microencapsulated islets, the graft function was achieved for 7.4 /- 3.1 weeks (mean /- standard error), as determined by elimination or reduction of exogenous insulin requirement. In three recipients, the fasting blood glucose levels were maintained at <=200 mg/dL without any exogenous insulin for a period of 6, 50, and 119 days. Circulating porcine C-peptide was detected in the sera of all dogs after transplantation of encapsulated islets. Immunohistologic examination revealed the presence of insulin-positive cells in the microcapsules. In contrast, in two dogs receiving nonencapsulated islets there was no graft function.
Conclusions: This preliminary study demonstrates that agarose-PSSa microencapsulated pig islets can survive and function for weeks or months in totally pancreatectomized diabetic dogs without immunosuppression.
(C) 2002 Lippincott Williams & Wilkins, Inc.