BACKGROUND: The increasing availability of genetically engineered pigs is steadily improving the results of pig organ and cell transplantation in non-human primates (NHPs). Current techniques offer knockout of pig genes and/or knockin of human genes. Knowledge of normal values of hematologic, biochemical, coagulation, and other parameters in healthy genetically engineered pigs and NHPs is important, particularly following pig organ transplantation in NHPs. Furthermore, information on parameters in various NHP species may prove important in selecting the optimal NHP model for specific studies. METHODS: We have collected hematologic, biochemical, and coagulation data on 71 α1,3-galactosyltransferase gene-knockout (GTKO) pigs, 18 GTKO pigs additionally transgenic for human CD46 (GTKO.hCD46), four GTKO.hCD46 pigs additionally transgenic for human CD55 (GTKO.hCD46.hCD55), and two GTKO.hCD46 pigs additionally transgenic for human thrombomodulin (GTKO.hCD46.hTBM). RESULTS: We report these data and compare them with similar data from wild-type pigs and the three major NHP species commonly used in biomedical research (baboons, cynomolgus, and rhesus monkeys) and humans, largely from previously published reports. CONCLUSIONS: Genetic modification of the pig (e.g., deletion of the Gal antigen and/or the addition of a human transgene) (i) does not result in abnormalities in hematologic, biochemical, or coagulation parameters that might impact animal welfare, (ii) seems not to alter metabolic function of vital organs, although this needs to be confirmed after their xenotransplantation, and (iii) possibly (though, by no means certainly) modifies the hematologic, biochemical, and coagulation parameters closer to human values. This study may provide a good reference for those working with genetically engineered pigs in xenotransplantation research and eventually in clinical xenotransplantation.
BACKGROUND: The increasing availability of genetically engineered pigs is steadily improving the results of pig organ and cell transplantation in non-human primates (NHPs). Current techniques offer knockout of pig genes and/or knockin of human genes. Knowledge of normal values of hematologic, biochemical, coagulation, and other parameters in healthy genetically engineered pigs and NHPs is important, particularly following pig organ transplantation in NHPs. Furthermore, information on parameters in various NHP species may prove important in selecting the optimal NHP model for specific studies. METHODS: We have collected hematologic, biochemical, and coagulation data on 71 α1,3-galactosyltransferase gene-knockout (GTKO) pigs, 18 GTKO pigs additionally transgenic for humanCD46 (GTKO.hCD46), four GTKO.hCD46pigs additionally transgenic for humanCD55 (GTKO.hCD46.hCD55), and two GTKO.hCD46pigs additionally transgenic for humanthrombomodulin (GTKO.hCD46.hTBM). RESULTS: We report these data and compare them with similar data from wild-type pigs and the three major NHP species commonly used in biomedical research (baboons, cynomolgus, and rhesus monkeys) and humans, largely from previously published reports. CONCLUSIONS: Genetic modification of the pig (e.g., deletion of the Gal antigen and/or the addition of a human transgene) (i) does not result in abnormalities in hematologic, biochemical, or coagulation parameters that might impact animal welfare, (ii) seems not to alter metabolic function of vital organs, although this needs to be confirmed after their xenotransplantation, and (iii) possibly (though, by no means certainly) modifies the hematologic, biochemical, and coagulation parameters closer to human values. This study may provide a good reference for those working with genetically engineered pigs in xenotransplantation research and eventually in clinical xenotransplantation.
Authors: Anna Casu; Gabriel J Echeverri; Rita Bottino; Dirk J van der Windt; Jing He; Burcin Ekser; Suyapa Ball; David Ayares; David K C Cooper Journal: Xenotransplantation Date: 2010 Mar-Apr Impact factor: 3.907
Authors: D J Van Der Windt; C Smetanka; C Macedo; J He; R Lakomy; R Bottino; B Ekser; G J Echeverri; D Metes; J N M Ijzermans; M Trucco; D K C Cooper; F G Lakkis Journal: Am J Transplant Date: 2010-04 Impact factor: 8.086
Authors: D J van der Windt; R Bottino; A Casu; N Campanile; C Smetanka; J He; N Murase; H Hara; S Ball; B E Loveland; D Ayares; F G Lakkis; D K C Cooper; M Trucco Journal: Am J Transplant Date: 2009-10-21 Impact factor: 8.086
Authors: A Casu; R Bottino; A N Balamurugan; H Hara; D J van der Windt; N Campanile; C Smetanka; D K C Cooper; M Trucco Journal: Diabetologia Date: 2007-10-25 Impact factor: 10.122
Authors: B Ekser; C Long; G J Echeverri; H Hara; M Ezzelarab; C C Lin; M E de Vera; R Wagner; E Klein; R F Wolf; D Ayares; D K C Cooper; B Gridelli Journal: Am J Transplant Date: 2009-12-23 Impact factor: 8.086
Authors: Hayato Iwase; Burcin Ekser; Vikas Satyananda; Jay Bhama; Hidetaka Hara; Mohamed Ezzelarab; Edwin Klein; Robert Wagner; Cassandra Long; Jnanesh Thacker; Jiang Li; Hao Zhou; Maolin Jiang; Santosh Nagaraju; Huidong Zhou; Massimiliano Veroux; Pietro Bajona; Martin Wijkstrom; Yi Wang; Carol Phelps; Nikolai Klymiuk; Eckhard Wolf; David Ayares; David K C Cooper Journal: Xenotransplantation Date: 2015-04-03 Impact factor: 3.907
Authors: Gregory R Stettler; Ernest E Moore; Hunter B Moore; Peter J Lawson; Miguel Fragoso; Geoffrey R Nunns; Christopher C Silliman; Anirban Banerjee Journal: J Surg Res Date: 2017-05-11 Impact factor: 2.192
Authors: John M Stewart; Alice F Tarantal; Wayne J Hawthorne; Evelyn J Salvaris; Philip J O'Connell; Mark B Nottle; Anthony J F d'Apice; Peter J Cowan; Mary Kearns-Jonker Journal: Xenotransplantation Date: 2014-05-08 Impact factor: 3.907
Authors: Huidong Zhou; Hayato Iwase; Roman F Wolf; Burcin Ekser; Mohamed Ezzelarab; Hidetaka Hara; Gary White; David K C Cooper Journal: Xenotransplantation Date: 2014-02-18 Impact factor: 3.907