Successful islet auto- and allotransplantation in diabetic pigs.
BACKGROUND
Because of its anatomical and physiological similarities to humans, the pig appears to be a suitable large animal model for preclinical studies of islet transplantation. The aim of this study was to investigate islet auto- and allotransplantation in a pig model with diabetes induced by total pancreatectomy.


METHODS
Porcine islets were isolated by a continuous digestion-filtration device at 32 degrees C and purified by a discontinuous iso-osmolar Ficoll-sodium-diatrizoate gradient on a Cobe 2991. The purified islets were autografted into the liver or the renal subcapsular space. The liver appears to be a more suitable site for the islet grafts than the renal subcapsular space, and the minimal amount of islets for reversal of diabetes is >5 microl/kg of body weight.


RESULTS
Persistent normoglycemia (fasting blood glucose level: 72.4+/-44.38 mg/dl) with a normal insulin secretion response to glucose stimulation was successfully achieved in five of six diabetic pigs by implanting a sufficient islet mass into the liver. Triple-drug immunosuppressive therapy with cyclosporine, azathioprine, and prednisolone did not prevent porcine islet allografts from experiencing early failure. However, the addition of 15-deoxyspergualin to the triple-drug immunosuppressive regimen significantly prolonged the function of the islet allografts. When antithymocyte globulin was added to the above-mentioned immunosuppressive drug regimen, the normoglycemic period was prolonged to more than 1 month (fasting blood glucose level: 75.4+/-17 mg/dl).


CONCLUSIONS
We conclude that autotransplantation with a sufficient islet mass can induce normoglycemia with a normal insulin secretion response to glucose stimulation in pancreatectomized diabetic pigs and that allotransplantation can be successfully achieved when 15-deoxyspergualin and antithymocyte globulin are combined with the triple-drug immunosuppression described above. However, this immunosuppressive protocol results in a high rate of infectious complications.
Department of Surgery, University of Rostock, Germany.
J
J
Mellert
B J
BJ
Hering
X
X
Liu
D
D
Brandhorst
H
H
Brandhorst
M
M
Brendel
E
E
Ernst
D
D
Gramberg
R G
RG
Bretzel
U T
UT
Hopt
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D005260:Female; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016381:Islets of Langerhans Transplantation; D010180:Pancreatectomy; D013552:Swine; D013556:Swine, Miniature; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D001786:Blood Glucose; D007166:Immunosuppressive Agents