Reduction of early graft loss after intraportal porcine islet transplantation in monkeys.
BACKGROUND
Pig islets constitute a possible resolution to the shortage of human islets for transplantation. After intraportal infusion of porcine islets in primates, many islets are lost through what has been termed the instant blood-mediated inflammatory reaction (IBMIR). We report on our experience with IBMIR.


METHODS
Ten monkeys underwent intraportal porcine islet transplantation. Immunosuppressive therapy was with conventional agents (n=3) or based on costimulation blockade (n=7). Treatment specific for IBMIR was administered in eight monkeys; two additional monkeys received no such therapy (group 1). Cobra venom factor completely inhibited complement activity in four (group 2) and dextran sulfate provided anticoagulation in four (group 3). Islet graft function was monitored by following blood glucose, insulin requirement, and porcine C-peptide values.


RESULTS
In monkeys that received neither cobra venom factor nor dextran sulfate (group 1), there was rapid destruction of islets indicated by severe hypoglycemia and the need for dextrose infusion; C-peptide levels were initially low and further reduction occurred within the first five days. In both groups 2 and 3, there was significantly less destruction of islets and some reversal of diabetes. However, when 40,000 IEQ/kg were infused, normoglycemia was lost within five days, but when 80,000 IEQ/kg were infused in one case, normoglycemia was more persistent. We observed that even when C-peptide levels were in the normal range for healthy nondiabetic pigs, these were not sufficient to maintain normoglycemia in the monkeys.


CONCLUSIONS
Although pretransplantation complement depletion or anticoagulation reduces porcine islet xenograft loss significantly, neither alone is sufficient to prevent IBMIR.
Rood
Pleunie P M
PP
Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Bottino
Rita
R
Balamurugan
A N
AN
Smetanka
Cindy
C
Ayares
David
D
Groth
Carl-Gustav
CG
Murase
Noriko
N
Cooper
David K C
DK
Trucco
Massimo
M
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D015941:Complement Hemolytic Activity Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008252:Macaca fascicularis / Q000276:immunology*; D008297:Male; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology
D000925:Anticoagulants; D001786:Blood Glucose; D002096:C-Peptide; D007166:Immunosuppressive Agents; D007328:Insulin