Reduced human platelet uptake by pig livers deficient in the asialoglycoprotein receptor 1 protein

Xenotransplantation
Leela L ParisA Joseph Tector

Abstract

The lethal thrombocytopenia that accompanies liver xenotransplantation is a barrier to clinical application. Human platelets are bound by the asialoglycoprotein receptor (ASGR) on pig sinusoidal endothelial cells and phagocytosed. Inactivation of the ASGR1 gene in donor pigs may prevent xenotransplantation-induced thrombocytopenia. Transcription activator-like effector nucleases (TALENs) were targeted to the ASGR1 gene in pig liver-derived cells. ASGR1 deficient pig cells were used for somatic cell nuclear transfer (SCNT). ASGR1 knock out (ASGR1-/-) fetal fibroblasts were used to produce healthy ASGR1 knock out piglets. Human platelet uptake was measured in ASGR1+/+ and ASGR1-/- livers. Targeted disruption of the ASGR1 gene with TALENs eliminated expression of the receptor. ASGR1-/- livers phagocytosed fewer human platelets than domestic porcine livers during perfusion. The use of TALENs in liver-derived cells followed by SCNT enabled the production of healthy homozygous ASGR1 knock out pigs. Livers from ASGR1-/- pigs exhibit decreased human platelet uptake. Deletion of the ASGR1 gene is a viable strategy to diminish platelet destruction in pig-to-human xenotransplantation.

References

Jan 1, 1982·Annual Review of Biochemistry·G Ashwell, J Harford
Feb 28, 2002·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·A Joseph TectorJean I Tchervenkov
Jul 5, 2002·Proceedings of the National Academy of Sciences of the United States of America·Lesley G ElliesJamey D Marth
May 20, 2008·Nature Medicine·Prabhjit K GrewalJamey D Marth
Sep 29, 2009·Nature Medicine·Viktoria RumjantsevaKarin M Hoffmeister
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
May 4, 2010·Nature Methods·Yannick DoyonMichael C Holmes
Aug 24, 2010·Current Opinion in Hematology·Renata GrozovskyHervé Falet
Oct 20, 2010·Xenotransplantation·Christopher BurlakA Joseph Tector
Aug 13, 2011·Transplantation·Ray K ChiharaChristopher Burlak
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Daniel F CarlsonScott C Fahrenkrug

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Citations

Feb 26, 2016·Transplantation·Peter J Cowan, Robert Rieben
Jan 28, 2016·Xenotransplantation·David K C CooperRita Bottino
Sep 15, 2015·The Journal of Pathology·David K C CooperDavid Ayares
Sep 1, 2015·International Journal of Surgery·Muhammad M MohiuddinChristopher G A McGregor
Jul 30, 2015·International Journal of Surgery·Peter J Cowan, Simon C Robson
Aug 2, 2015·International Journal of Surgery·James R ButlerA Joseph Tector
Jul 21, 2015·International Journal of Surgery·Burcin EkserA Joseph Tector
Aug 27, 2015·International Journal of Surgery·Guerard W ByrneMichael E Breimer
Jul 17, 2015·Xenotransplantation·Christopher BurlakBenjamin P Beaton
Mar 11, 2016·Annals of Surgery·Joseph Tector
Aug 16, 2016·Current Opinion in Organ Transplantation·Wayne J HawthorneHelen E Thomas
Jul 19, 2016·Transplantation·David K C CooperBurcin Ekser
Feb 6, 2017·Cell Transplantation·Zhengzhao LiuLisha Mou
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
Feb 16, 2019·Xenotransplantation·Xuan ZhangKefeng Dou
Oct 10, 2018·Current Opinion in Organ Transplantation·Arielle CimenoJohn C LaMattina
Feb 11, 2020·Frontiers in Immunology·Tianyu LuChuan Qin
Apr 13, 2021·The Journal of Reproduction and Development·Fuminori TaniharaTakeshige Otoi
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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