Silencing Porcine CMAH and GGTA1 Genes Significantly Reduces Xenogeneic Consumption of Human Platelets by Porcine Livers

Transplantation
James Russell ButlerA Joseph Tector

Abstract

A profound thrombocytopenia limits hepatic xenotransplantation in the pig-to-primate model. Porcine livers also have shown the ability to phagocytose human platelets in the absence of immune-mediated injury. Recently, inactivation of the porcine ASGR1 gene has been shown to decrease this phenomenon. Inactivating GGTA1 and CMAH genes has reduced the antibody-mediated barrier to xenotransplantation; herein, we describe the effect that these modifications have on xenogeneic consumption of human platelets in the absence of immune-mediated graft injury. Wild type (WT), ASGR1, GGTA1, and GGTA1CMAH knockout pigs were compared for their xenogeneic hepatic consumption of human platelets. An in vitro assay was established to measure the association of human platelets with liver sinusoidal endothelial cells (LSECs) by immunohistochemistry. Perfusion models were used to measure human platelet uptake in livers from WT, ASGR1, GGTA1, and GGTA1 CMAH pigs. GGTA1, CMAH LSECs exhibited reduced levels of human platelet binding in vitro when compared with GGTA1 and WT LSECs. In a continuous perfusion model, GGTA1 CMAH livers consumed fewer human platelets than GGTA1 and WT livers. GGTA1 CMAH livers also consumed fewer human platelets than ASGR1 li...Continue Reading

References

Sep 29, 2001·Kidney International·B SoinP J Friend
May 20, 2008·Nature Medicine·Prabhjit K GrewalJamey D Marth
Jun 7, 2008·Nature Medicine·Cornelis van't Veer, Tom van der Poll
Jan 1, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·B EkserB Gridelli
Aug 24, 2010·Current Opinion in Hematology·Renata GrozovskyHervé Falet
Oct 20, 2010·Xenotransplantation·Christopher BurlakA Joseph Tector
Jan 25, 2011·Nature Reviews. Cancer·Laurie J Gay, Brunhilde Felding-Habermann
Oct 25, 2011·Lancet·Burcin EkserDavid K C Cooper
Sep 12, 2014·Xenotransplantation·Mohamed B EzzelarabDavid K Cooper
Jan 30, 2015·JAMA Surgery·Abbas RanaRainer W G Gruessner
Apr 3, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·D R SalomonUNKNOWN AST/ASTS Incentives Workshop Group (IWG)

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Citations

Jul 28, 2016·Xenotransplantation·Christopher Burlak
Aug 16, 2016·Current Opinion in Organ Transplantation·Peter J Cowan
Jul 19, 2016·Transplantation·David K C CooperBurcin Ekser
Nov 9, 2016·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Jeremy R Chapman
Apr 12, 2017·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·P J Cowan, A J Tector
Oct 24, 2017·Xenotransplantation·Beth M FrenchAgnes M Azimzadeh
Nov 28, 2018·Current Opinion in Organ Transplantation·Peter J CowanMark B Nottle
Feb 16, 2019·Xenotransplantation·Xuan ZhangKefeng Dou
Dec 3, 2016·Transplantation·David K C CooperRichard N Pierson
Oct 10, 2018·Current Opinion in Organ Transplantation·Arielle CimenoJohn C LaMattina
Feb 26, 2016·Transplantation·Peter J Cowan, Robert Rieben
Jul 13, 2017·Molecular Biotechnology·Magdalena HryhorowiczDaniel Lipiński
Aug 25, 2020·Current Opinion in Organ Transplantation·Malcolm MacConmaraParsia A Vagefi
Feb 11, 2020·Frontiers in Immunology·Tianyu LuChuan Qin
Jan 8, 2021·International Journal of Immunogenetics·Marco Carvalho-OliveiraConstanca Figueiredo
Apr 11, 2020·Advanced Drug Delivery Reviews·Dong NiuGeorge M Church
Apr 4, 2021·International Journal of Molecular Sciences·Natalia RyczekRyszard Słomski
Jul 8, 2021·Transgenic Research·Joohyun ShimKimyung Choi
Aug 17, 2021·Animal Biotechnology·Hak Myong ChoeXi-Jun Yin
Sep 14, 2017·Current Opinion in Organ Transplantation·Burcin EkserDavid K C Cooper
Mar 4, 2021·Transplantation·Vladimir LammDavid K C Cooper

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