title: Outcomes of alpha 1,3-GT-knockout porcine heart transplants into a preclinical nonhuman primate model.
abstract: BACKGROUND
  Solid organ xenotransplantation is a potential solution to current organ shortages in allotransplantation. We performed four heart transplantations from alpha1, 3-galactosyltransferase gene-knockout (GT-KO) pigs to cynomolgus monkeys and monitored immunological parameters before and after transplantation.
  
  
  METHODS
  After blood typing of the cynomolgus monkeys, we assessed the binding activity of immunoglobulin G (IgG) and IgM of monkey serum and serum toxicity toward porcine peripheral blood mononuclear cells (PBMCs) using flow cytometry. Immunosuppressive protocols consisted of anti-thymocyte globulin (25 mg/kg), rituximab (20 mg/kg), anti-CD154mAb (20 mg/kg), cobra venom factor (0.05 mg/kg), tacrolimus, and steroid. Cynomolgus monkeys with A or AB blood type with the lowest antibody binding and serum toxicity activity on porcine PBMCs were selected as recipients.
  
  
  RESULTS
  Absolute numbers of CD3(+) T cells, CD20(+) B cells, and CD3(+)CD95(+) memory T cells in the peripheral blood were suppressed upto 24 days after transplantation. Interferon gamma production of T cells in response to porcine antigens were also significantly suppressed. Heart xenografts from GT-KO pigs survived for upto 24 days without pathologic evidence of rejection.
  
  
  CONCLUSIONS
  We successfully performed 4 heart xenotransplantations using GT-KO pigs. We overcame hyperacute rejection by using GT-KO pigs, and all of the heart xenografts from the GT-KO pigs survived between 11 and 24 days without pathologic evidence of rejection, disseminated intravascular coagulation, or consumptive coagulopathy; however, we need to optimize protocols for immune modulation and postoperative care to attain long-term survival of solid organ xenografts.
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: H K
authors.initials: HK
authors.lastname: Chee
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Hwang
authors.forename: K H
authors.initials: KH
authors.lastname: Han
authors.forename: J
authors.initials: J
authors.lastname: Kang
authors.forename: J H
authors.initials: JH
authors.lastname: Park
authors.forename: J S
authors.initials: JS
authors.lastname: Kim
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: S A
authors.initials: SA
authors.lastname: Ock
authors.forename: M H
authors.initials: MH
authors.lastname: Park
authors.forename: K S
authors.initials: KS
authors.lastname: Park
authors.forename: B C
authors.initials: BC
authors.lastname: Lee
authors.forename: L
authors.initials: L
authors.lastname: Byeongchun
authors.forename: K
authors.initials: K
authors.lastname: Cho
authors.forename: J
authors.initials: J
authors.lastname: Noh
authors.forename: W
authors.initials: W
authors.lastname: Park
authors.forename: I J
authors.initials: IJ
authors.lastname: Yun
authors.forename: C
authors.initials: C
authors.lastname: Ahn
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005700:Galactosyltransferases / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006085:Graft Survival; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008252:Macaca fascicularis; D013552:Swine
chemical_list: D007166:Immunosuppressive Agents; D005700:Galactosyltransferases