title: Results of life-supporting galactosyltransferase knockout kidneys in cynomolgus monkeys using two different sources of galactosyltransferase knockout Swine.
abstract: BACKGROUND
  Various durations of survival have been observed in the xenotransplantation of life-supporting α-1,3-galactosyltransferase knockout (GalT-KO) porcine kidneys into nonhuman primates. Although others have demonstrated loss of GalT-KO-transplanted kidneys within 2 weeks, we have reported an average survival of 51 days with the cotransplantation of the kidney and vascularized thymus and an average of 29 days with the kidney alone. To determine the factors responsible for this difference in survival time, we performed xenogeneic kidney transplantations into cynomolgus monkeys with an anti-CD40L-based regimen using two different strains of GalT-KO swine, one derived from MGH miniature swine and the other obtained from Meji University.
  
  
  METHODS
  Eight cynomolgus moneys received GalT-KO kidneys. Three kidney grafts were from Massachusetts General Hospital (MGH)-Nippon Institute for Biological Science (NIBS) GalT-KO pigs and five GalT-KO grafts were from MEIJI GalT-KO swine. All cynomolgus recipients were treated identically.
  
  
  RESULTS
  Recipients of kidneys from the MGH GalT-KO kidneys swine, produced by nuclear transfer in Japan, survived an average of 28.7 days, whereas recipients of MEIJI GalT-KO kidneys swine survived an average of 9.2 days. Among the differences between these two groups, one potentially revealing disparity was that the MEIJI swine were positive for porcine cytomegalovirus, whereas the MGH-derived swine were negative.
  
  
  CONCLUSIONS
  This is the first study comparing renal xenotransplantation from two different sources of GalT-KO swine into nonhuman primates at a single center. The results demonstrate that porcine cytomegalovirus may be responsible for early loss of GalT-KO swine kidney xenografts.
authors.affiliation: 1 Division of Organ Replacement and Xenotransplantation Surgery, Center for Advanced Biomedical Science and Swine Research, Kagoshima University, Kagoshima, Japan. 2 Faculty of Applied Biological Sciences, Gifu University, Gifu, Japan. 3 Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA. 4 Research and Development Department, Nippon Institute for Biological Science, Tokyo, Japan. 5 Laboratory of Developmental Engineering, Meiji University School of Agriculture, Tokyo, Japan. 6 Address correspondence to: Kazuhiko Yamada, M.D., Ph.D., Center for Advanced Biomedical Science and Swine Research, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Sekijima
authors.forename: Shiori
authors.initials: S
authors.lastname: Waki
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sahara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tasaki
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wilkinson
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Villani
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Shimatsu
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nakano
authors.forename: Hitomi
authors.initials: H
authors.lastname: Matsunari
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagashima
authors.forename: Jay A
authors.initials: JA
authors.lastname: Fishman
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D003404:Creatinine / Q000097:blood; D003586:Cytomegalovirus Infections / Q000635:transmission; D005260:Female; D005700:Galactosyltransferases / Q000502:physiology*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation; D008252:Macaca fascicularis; D008297:Male; D013552:Swine; D014183:Transplantation, Heterologous
chemical_list: D000906:Antibodies; D003404:Creatinine; D005700:Galactosyltransferases; C047006:N-acetyllactosaminide alpha-1,3-galactosyltransferase