Xenotransplantation of pig islets in diabetic dogs with use of a microcapsule composed of agarose and polystyrene sulfonic acid mixed gel.
BACKGROUND
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.


OBJECTIVE
To investigate the efficacy of agarose-PSSa microencapsulated pig islets in reversing diabetes in a large animal model.


METHODS
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 < or = 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.
Kin
Tatsuya
T
First Department of Surgery, Nara Medical University, Nara, Japan. tkin@gpu.srv.ualberta.ca
Iwata
Hiroo
H
Aomatsu
Yukio
Y
Ohyama
Takao
T
Kanehiro
Hiromichi
H
Hisanaga
Michiyoshi
M
Nakajima
Yoshiyuki
Y
D000818:Animals; D001786:Blood Glucose; D002214:Capsules; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D004285:Dogs; D005782:Gels; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D010180:Pancreatectomy; D010865:Pilot Projects; D011137:Polystyrenes; D012685:Sepharose; D013552:Swine; D014183:Transplantation, Heterologous
D001786:Blood Glucose; D002214:Capsules; D005782:Gels; D011137:Polystyrenes; C003321:polystyrene sulfonic acid; D012685:Sepharose