期刊
TRANSPLANTATION
卷 90, 期 5, 页码 483-493出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e3181e98d51
关键词
alpha 1,3-Galactosylransferase gene-knockout; Acute liver failure; Baboon; Coagulation; Coagulation factors; Liver; Pig; Genetically modified; Xenotransplantation
资金
- NIH [U01 AI068642, R21 A1074844, RR012317-09]
- University of Pittsburgh
- Revivicor, Inc., Blacksburg, VA
- American Transplant Congress
- International Xenotransplantation Association Congress
Background. If bridging to allo-transplantation (Tx) is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods. We have studied hepatic function in baboons after Tx of livers from alpha 1,3-galactosyltransferase gene-knockout (GTKO, n = 1) or GTKO pigs transgenic for CD46 (GTKO/CD46, n = 5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In four baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results. Recipient baboons died or were euthanized after 4 to 7 days after internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, and plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions. After the Tx of genetically engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near normal; (2) there was evidence for production of pig proteins, including coagulation factors; and (3) these appeared to function adequately in baboons although interspecies compatibility of such proteins remains to be confirmed.
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