title: Reduction of early graft loss after intraportal porcine islet transplantation in monkeys.
abstract: 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.
authors.affiliation: Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Pleunie P M
authors.initials: PP
authors.lastname: Rood
authors.forename: Rita
authors.initials: R
authors.lastname: Bottino
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.forename: Cindy
authors.initials: C
authors.lastname: Smetanka
authors.forename: David
authors.initials: D
authors.lastname: Ayares
authors.forename: Carl-Gustav
authors.initials: CG
authors.lastname: Groth
authors.forename: Noriko
authors.initials: N
authors.lastname: Murase
authors.forename: David K C
authors.initials: DK
authors.lastname: Cooper
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
mesh_terms: 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
chemical_list: D000925:Anticoagulants; D001786:Blood Glucose; D002096:C-Peptide; D007166:Immunosuppressive Agents; D007328:Insulin