Initial in vitro studies on tissues and cells from GTKO/CD46/NeuGcKO pigs

The impact that the absence of expression of NeuGc in pigs might have on pig organ or cell transplantation in humans has been studied in vitro, but only using red blood cells (pRBCs) and peripheral blood mononuclear cells (pPBMCs) as the target cells for immune assays. We have extended this work in various in vitro models and now report our initial results.

[1]  D. Cooper,et al.  Expression of NeuGc on Pig Corneas and Its Potential Significance in Pig Corneal Xenotransplantation , 2016, Cornea.

[2]  M. Ezzelarab,et al.  Transgenic expression of human CD46: does it reduce the primate T‐cell response to pig endothelial cells? , 2015, Xenotransplantation.

[3]  R. Pierson,et al.  Early graft failure of GalTKO pig organs in baboons is reduced by expression of a human complement pathway‐regulatory protein , 2015, Xenotransplantation.

[4]  R. Bottino,et al.  In vitro exposure of pig neonatal isletlike cell clusters to human blood , 2015, Xenotransplantation.

[5]  M. Tector,et al.  Evaluation of human and non‐human primate antibody binding to pig cells lacking GGTA1/CMAH/β4GalNT2 genes , 2015, Xenotransplantation.

[6]  M. Wijkstrom,et al.  Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs. , 2015, Transplant immunology.

[7]  Christopher J. Gregg,et al.  A red meat-derived glycan promotes inflammation and cancer progression , 2014, Proceedings of the National Academy of Sciences.

[8]  M. Trucco,et al.  Pig‐to‐Monkey Islet Xenotransplantation Using Multi‐Transgenic Pigs , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[9]  C. McGregor,et al.  Cloning and expression of porcine β1,4 N-acetylgalactosaminyl transferase encoding a new xenoreactive antigen , 2014, Xenotransplantation.

[10]  P. Gagneux,et al.  Parallel evolution of a self-signal: humans and new world monkeys independently lost the cell surface sugar Neu5Gc , 2014, Immunogenetics.

[11]  M. Tector,et al.  Reduced Binding of Human Antibodies to Cells From GGTA1/CMAH KO Pigs , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[12]  M. Tector,et al.  Erythrocytes from GGTA1/CMAH knockout pigs: implications for xenotransfusion and testing in non‐human primates , 2014, Xenotransplantation.

[13]  K. Isse,et al.  Distribution of Non-Gal Antigens in Pig Cornea: Relevance to Corneal Xenotransplantation , 2014, Cornea.

[14]  A. Varki,et al.  Long-Term IgG Response to Porcine Neu5Gc Antigens without Transmission of PERV in Burn Patients Treated with Porcine Skin Xenografts , 2013, The Journal of Immunology.

[15]  D. Cooper,et al.  Comparison of Proliferative Capacity of Genetically-Engineered Pig and Human Corneal Endothelial Cells , 2012, Ophthalmic Research.

[16]  R. Bottino,et al.  Early Islet Damage after Direct Exposure of Pig Islets to Blood: Has Humoral Immunity Been Underestimated? , 2012, Cell transplantation.

[17]  M. Ezzelarab,et al.  Costimulation blockade in pig artery patch xenotransplantation – a simple model to monitor the adaptive immune response in nonhuman primates , 2012, Xenotransplantation.

[18]  L. Rigatti,et al.  T-Cell-Based Immunosuppressive Therapy Inhibits the Development of Natural Antibodies in Infant Baboons , 2012, Transplantation.

[19]  H. Tazelaar,et al.  Human CD55 Expression Blocks Hyperacute Rejection and Restricts Complement Activation in Gal Knockout Cardiac Xenografts , 2012, Transplantation.

[20]  H. Ohdan,et al.  Deficiency of N‐glycolylneuraminic acid and Galα1‐3Galβ1‐4GlcNAc epitopes in xenogeneic cells attenuates cytotoxicity of human natural antibodies , 2010, Xenotransplantation.

[21]  N. Bovin,et al.  Investigation of potential carbohydrate antigen targets for human and baboon antibodies , 2010, Xenotransplantation.

[22]  H. Takematsu,et al.  Immunological Property of Antibodies against N-Glycolylneuraminic Acid Epitopes in Cytidine Monophospho–N-Acetylneuraminic Acid Hydroxylase-Deficient Mice , 2010, The Journal of Immunology.

[23]  D. Cooper,et al.  Genetically engineered pig red blood cells for clinical transfusion: initial in vitro studies , 2009, Transfusion.

[24]  A. D'apice,et al.  The vascular and coagulation issues in xenotransplantation , 2009, Current opinion in organ transplantation.

[25]  H. Tai,et al.  In vitro investigation of pig cells for resistance to human antibody‐mediated rejection , 2008, Transplant international : official journal of the European Society for Organ Transplantation.

[26]  H. Tai,et al.  Late onset of development of natural anti‐nonGal antibodies in infant humans and baboons: implications for xenotransplantation in infants , 2007, Transplant international : official journal of the European Society for Organ Transplantation.

[27]  U. Galili,et al.  Replacement of Human Anterior Cruciate Ligaments with Pig Ligaments: A Model for Anti-Non-Gal Antibody Response in Long-Term Xenotransplantation , 2007, Transplantation.

[28]  R. Bottino,et al.  Isolation outcome and functional characteristics of young and adult pig pancreatic islets for transplantation studies , 2007, Xenotransplantation.

[29]  M. Ezzelarab,et al.  Allosensitized humans are at no greater risk of humoral rejection of GT‐KO pig organs than other humans , 2006, Xenotransplantation.

[30]  D. Cooper,et al.  How strong is the T cell response in the pig‐to‐primate model? , 2005, Xenotransplantation.

[31]  Akimasa Nakao,et al.  Are N‐glycolylneuraminic acid (Hanganutziu–Deicher) antigens important in pig‐to‐human xenotransplantation? , 2004, Xenotransplantation.

[32]  B. Loveland,et al.  Characterization of a CD46 transgenic pig and protection of transgenic kidneys against hyperacute rejection in non‐immunosuppressed baboons , 2004, Xenotransplantation.

[33]  A. Varki,et al.  Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[34]  Takaaki Kobayashi,et al.  Release of pig leukocytes during pig kidney perfusion and characterization of pig lymphocyte carbohydrate xenoantigens , 2003, Xenotransplantation.

[35]  A. Zhu,et al.  Anti‐N‐glycolylneuraminic acid antibodies identified in healthy human serum , 2002, Xenotransplantation.

[36]  O. Korsgren,et al.  Isolated Human Islets Trigger an Instant Blood Mediated Inflammatory Reaction: Implications for Intraportal Islet Transplantation as a Treatment for Patients with Type 1 Diabetes , 2000, Upsala journal of medical sciences.

[37]  C. Pourcel,et al.  Simultaneous expression by porcine aorta endothelial cells of glycosphingolipids bearing the major epitope for human xenoreactive antibodies (Galα1–3Gal), blood group H determinant andN-glycolylneuraminic acid , 1996, Glycoconjugate Journal.

[38]  R. Michler,et al.  Newborn baboon serum anti-alpha galactosyl antibody levels and cytotoxicity to cultured pig kidney (PK15) cells. , 1995, Transplantation.

[39]  R. Oriol,et al.  Evidence that intravenously administered alpha-galactosyl carbohydrates reduce baboon serum cytotoxicity to pig kidney cells (PK15) and transplanted pig hearts. , 1994, Transplantation.

[40]  R. Oriol,et al.  Genetically engineered pigs , 1993, The Lancet.

[41]  R. Oriol,et al.  Identification of alpha-galactosyl and other carbohydrate epitopes that are bound by human anti-pig antibodies: relevance to discordant xenografting in man. , 1993, Transplant immunology.

[42]  D. Cooper,et al.  Identification of carbohydrate structures that bind human antiporcine antibodies: implications for discordant xenografting in humans. , 1992, Transplantation proceedings.

[43]  S. Shohet,et al.  Man, apes, and Old World monkeys differ from other mammals in the expression of alpha-galactosyl epitopes on nucleated cells. , 1988, The Journal of biological chemistry.

[44]  J. Griffiss,et al.  Interaction between human natural anti-alpha-galactosyl immunoglobulin G and bacteria of the human flora , 1988, Infection and immunity.

[45]  A. Rose,et al.  Effects of cyclosporine and antibody adsorption on pig cardiac xenograft survival in the baboon. , 1988, The Journal of heart transplantation.

[46]  A. Rose,et al.  Hyperacute rejection in a discordant (pig to baboon) cardiac xenograft model. , 1986, The Journal of heart transplantation.

[47]  D. Cooper,et al.  Regulation of human platelet aggregation by genetically modified pig endothelial cells and thrombin inhibition , 2014, Xenotransplantation.

[48]  C. Burlak,et al.  Double knockout pigs deficient in N‐glycolylneuraminic acid and Galactose α‐1,3‐Galactose reduce the humoral barrier to xenotransplantation , 2013, Xenotransplantation.

[49]  D. Cooper,et al.  The effect of Gal expression on pig cells on the human T‐cell xenoresponse , 2012, Xenotransplantation.

[50]  A. Varki,et al.  Potential impact of the non‐human sialic acid N‐glycolylneuraminic acid on transplant rejection risk , 2011, Xenotransplantation.

[51]  N. Mueller,et al.  Heart transplantation in baboons using α1,3-galactosyltransferase gene-knockout pigs as donors: initial experience , 2005, Nature Medicine.

[52]  D. Sachs,et al.  Marked prolongation of porcine renal xenograft survival in baboons through the use of α1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue , 2005, Nature Medicine.

[53]  T. Starzl,et al.  Production of alpha 1,3-galactosyltransferase-deficient pigs. , 2003, Science.

[54]  U. Galili.  Evolution of alpha 1,3galactosyltransferase and of the alpha-Gal epitope. , 1999, Sub-cellular biochemistry.

[55]  U. Galili.  Evolution of α1,3Galactosyltransferase and of the α-Gal Epitope , 1999 .

[56]  D. B. Carter,et al.  Production of (cid:1) -1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations , 2022 .

[57]  S. H. A. Chen,et al.  Production of α1,3-Galactosyltransferase-Deficient Pigs , 2002, Science.