Document Detail


Long-term survival of nonhuman primates receiving life-supporting transgenic porcine kidney xenografts.
MedLine Citation:
PMID:  10919569     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Recently, there has been a resumed interest in clinical xenotransplantation using pig organs. However, no data are available yet regarding the capacity of porcine organs to sustain the life of a primate beyond the first month. We have attempted to obtain long-term survival of nonhuman primates using human decay-accelerating factor (hDAF) transgenic pig organs and an immunosuppressive strategy particularly aimed at neutralizing the humoral component of the immune response. METHODS: hDAF transgenic or control kidneys were transplanted into 14 bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis) that underwent splenectomy and were immunosuppressed with cyclosporine A, cyclophosphamide, and steroids. All animals also received recombinant erythropoietin. Postoperatively, the primates were monitored daily. Laboratory evaluations included serum biochemistry, hematology, and measurements of hemolytic antipig antibodies. To assess the role of splenectomy in the control of humoral response, historical data were also used from a group of monkeys (n=7) that received the same immunosuppressive regimen and an hDAF transgenic porcine kidney but did not have splenectomy or receive recombinant erythropoietin. RESULTS: This immunosuppressive approach obtained the longest survival time (78 days) described to date of a primate receiving a life-supporting porcine renal xenograft. Furthermore, four of nine animals in this series survived for 50 days or more. Most biochemical measurements in this study (including plasma urea, creatinine, sodium, and potassium concentrations) remained within normal ranges for several weeks in all of the longest-surviving animals. CONCLUSIONS: Normalization of renal function (urea and creatinine) in primate recipients of porcine renal xenografts suggests that pig kidneys may be suitable for future clinical xenotransplantation. Additional immunosuppressive approaches, specifically designed to prevent humorally mediated immunological damage, should be explored to further prolong survival of primates that have received porcine xenografts.
Authors:
E Cozzi; F Bhatti; M Schmoeckel; G Chavez; K G Smith; A Zaidi; J R Bradley; S Thiru; M Goddard; C Vial; D Ostlie; J Wallwork; D J White; P J Friend
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Transplantation     Volume:  70     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2000 Jul 
Date Detail:
Created Date:  2000-08-10     Completed Date:  2000-08-10     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  15-21     Citation Subset:  IM    
Affiliation:
Transplant Unit, Imutran Ltd, Cambridge, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Antigens, CD55 / genetics,  physiology*
Female
Graft Rejection
Kidney Transplantation / mortality*
Macaca fascicularis
Male
Survivors
Swine
Transplantation, Heterologous*
Chemical
Reg. No./Substance:
0/Antigens, CD55

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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