Journal
XENOTRANSPLANTATION
Volume 22, Issue 4, Pages 317-324Publisher
WILEY
DOI: 10.1111/xen.12178
Keywords
diabetes mellitus; genetically engineered; instant blood-mediated inflammatory reaction; islets; neonatal; pigs; xenotransplantation
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Funding
- Department of Defense [W81XWH-06-1-0317]
- JDRF [6-2005-1180]
- NIH [U19 AI090959-01, U01 AI068642, R21 A1074844]
- Revivicor, Inc., Blacksburg, VA
- University of Pittsburgh
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BackgroundPig islet grafts have been successful in treating diabetes in animal models. One remaining question is whether neonatal pig isletlike cell clusters (NICC) are resistant to the early loss of islets from the instant blood-mediated inflammatory reaction (IBMIR). MethodsNeonatal isletlike cell clusters were harvested from three groups of piglets(i) wild-type (genetically unmodified), (ii) 1,3-galactosyltransferase gene-knockout (GTKO)/CD46, and (iii) GTKO/CD46/CD39. NICC samples were mixed with human blood invitro, and the following measurements were madeantibody binding; complement activation; speed of islet-induced coagulation; C-peptide; glutamic acid decarboxylase (GAD65) release; viability. ResultsTime to coagulation and viability were both reduced in all groups compared to freshly drawn non-anticoagulated human blood and autologous combinations, respectively. Antibody binding to the NICC occurred in all groups. ConclusionsNeonatal isletlike cell clusters were subject to humoral injury with no difference associated to their genetic characteristics.
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