Journal
EXPERT REVIEW OF CLINICAL IMMUNOLOGY
Volume 8, Issue 7, Pages 621-634Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1586/ECI.12.56
Keywords
alpha 1,3-galactosyltransferase gene-knockout; hCD46; liver; liver failure; nonhuman primate; pig; xenotransplantation
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Funding
- NIH NIAID [T32 AI 074490]
- NIH [U19 AI090959-01, 5R01DK066160-05]
- University of Pittsburgh
- Revivicor, Inc., Blacksburg, VA, USA
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Expert Rev. Clin. Immunol. 8(7), 621-634 (2012) Pigs are currently the preferred species for future organ xenotransplantation. With advances in the development of genetically modified pigs, clinical xenotransplantation is becoming closer to reality. In preclinical studies (pig-to-nonhuman primate), the xenotransplantation of livers from pigs transgenic for human CD55 or from alpha 1,3-galactosyltransferase gene-knockout pigs+/- transgenic for human CD46, is associated with survival of approximately 7-9 days. Although hepatic function, including coagulation, has proved to be satisfactory, the immediate development of thrombocytopenia is very limiting for pig liver xenotransplantation even as a 'bridge' to allotransplantation. Current studies are directed to understand the immunobiology of platelet activation, aggregation and phagocytosis, in particular the interaction between platelets and liver sinusoidal endothelial cells, hepatocytes and Kupffer cells, toward identifying interventions that may enable clinical application.
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