Investigation of red blood cells from alpha1,3-galactosyltransferase-knockout pigs for human blood transfusion

Transfusion
F J RouhaniD K C Cooper

Abstract

Pigs are a potential source of red blood cells (RBCs) for transfusion into humans, but the presence of galactose-alpha1,3-galactose (Gal) epitopes on their surface, against which humans have anti-Gal, has been perceived as a major barrier. alpha1,3-Galactosyltransferase gene-knockout pigs, which do not express Gal epitopes on RBCs (Gal-/-), have recently become available. In vitro, RBCs from Gal-/- pigs were exposed to sera from naïve humans or baboons or from baboons previously sensitized to pig antigens; immunoglobulin binding was measured by flow cytometry, and cytotoxicity, by a hemolytic assay. In vivo, relatively small numbers of Gal-/- RBCs were transfused into two nonsensitized untreated baboons. The survival of pig RBCs was detected by flow cytometry. In vitro, binding of immunoglobulin (Ig) M from naïve human or baboon sera was detected to Gal-/- RBCs but was significantly less than to Gal+/+ RBCs; IgG binding to Gal-/- RBCs was absent or minimal. Sera had minimal cytotoxicity to Gal-/- RBCs compared to Gal+/+ RBCs. Sensitized baboon sera demonstrated much higher IgG binding to Gal-/- RBCs and increased cytotoxicity, but again these were less than to Gal+/+ RBCs. In vivo, the transfusion of relatively small volumes of...Continue Reading

References

Mar 5, 2002·Nature Biotechnology·Yifan DaiDavid L Ayares
Jun 13, 2002·Xenotransplantation·Jürgen H BluschUlrich Martin
Oct 10, 2002·Xenotransplantation·Alex Zhu, Rosa Hurst
Nov 15, 2002·Transfusion·Leslie A MacLarenVivian C McAlister
Dec 21, 2002·Science·Carol J PhelpsDavid L Ayares
Jul 25, 2003·Human Immunology·Diana MetesNoriko Murase
Sep 3, 2003·Xenotransplantation·David K C Cooper
Feb 14, 2004·Xenotransplantation·Jan M EckermannDavid K C Cooper
Jun 16, 2004·Xenotransplantation·F J M F Dor, D K C Cooper

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Citations

Jan 21, 2012·Current Opinion in Organ Transplantation·Hui Wang, Yong-Guang Yang
Dec 16, 2004·Xenotransplantation·Michael A Rees
Dec 16, 2004·Xenotransplantation·Reto M Baertschiger, Leo H Buhler
Jan 28, 2016·Xenotransplantation·David K C CooperRita Bottino
Jun 2, 2010·Clinics in Laboratory Medicine·David K C CooperMark Yazer
Jun 7, 2005·Transfusion·Jane L Swanson, Laura Cooling
May 11, 2007·Xenotransplantation·Françoise A RouxJack-Yves Deschamps
May 11, 2007·Xenotransplantation·Françoise A RouxJack-Yves Deschamps
Dec 10, 2014·Journal of Applied Genetics·J ZeylandR Słomski
Mar 5, 2016·Glycobiology·David K C Cooper

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