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Successful
long-term survival of pancreatic islet allografts in spontaneous or
pancreatectomy-induced diabetes in dogs. Cyclosporine-induced immune
unresponsiveness
R Cutfield, F L Shienvold, Z Latif, D H Mintz Abstract
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Abstract
Nineteen pancreatectomized beagles and three spontaneously diabetic dogs were
recipients of canine islet allografts from one or more unrelated donors. The
islets, enriched 30-45-fold for endocrine cells and contained in a packed cell
volume of less than 1.5 ml, were engrafted in the livers of recipient animals.
Treatment of diabetic recipients with cyclosporine (CsA) was begun 3-5 days
before islet transplantation and the initial dosage was adjusted to attain and
maintain CsA serum trough levels between 400 and 600 ng/ml. Five dogs with CsA
levels less than this (155 +/- 35 SEM ng/ml) at the time of transplantation
promptly rejected their grafts, whereas rejection was encountered in only 1 of
17 diabetic animals in which the initial level exceeded 400 ng/ml. CsA was
discontinued 30, 60, or 90 days after continuous therapy in 10 animals. Graft
failure was observed 2 mo after stopping CsA in 1 animal and 5 mo in the
other. Eight other islet allograft recipients have sustained fasting
euglycemia for 7 and 8 mo in 2 and for at least 2 mo in the remainder. These
results demonstrate that short-term CsA therapy prolongs survival of islet
allografts and induces a state of immune unresponsiveness to islet
alloantigens in dogs with experimental and spontaneous diabetes. The findings
are unique for a nonrodent mammal and thus hold promise that similar results
may be achieved for islet allografts of other mammalian species, including
humans.
Reference
DIABETES , 34(8):825-828
1985
Updated January 2016
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