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Yamamoto, Takayuki; Hara, Hidetaka; Foote, Jeremy; Wang, Liaoran; Li, Qi; Klein, Edwin C.; Schuurman, Hendrik Jan; Zhou, Hongmin; Li, Juan; Tector, A. Joseph; Zhang, Zhongqiang; Ezzelarab, Mohamed; Lovingood, Ray; Ayares, David; Eckhoff, Devin E.; Cooper, David K.C.; Iwase, Hayato

Life-supporting Kidney Xenotransplantation From Genetically Engineered Pigs in Baboons: A Comparison of Two Immunosuppressive Regimens

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  • Media type: E-Article
  • Title: Life-supporting Kidney Xenotransplantation From Genetically Engineered Pigs in Baboons: A Comparison of Two Immunosuppressive Regimens
  • Contributor: Yamamoto, Takayuki; Hara, Hidetaka; Foote, Jeremy; Wang, Liaoran; Li, Qi; Klein, Edwin C.; Schuurman, Hendrik Jan; Zhou, Hongmin; Li, Juan; Tector, A. Joseph; Zhang, Zhongqiang; Ezzelarab, Mohamed; Lovingood, Ray; Ayares, David; Eckhoff, Devin E.; Cooper, David K.C.; Iwase, Hayato
  • imprint: Ovid Technologies (Wolters Kluwer Health), 2019
  • Published in: Transplantation
  • Language: English
  • DOI: 10.1097/tp.0000000000002796
  • ISSN: 0041-1337
  • Origination:
  • Footnote:
  • Description: <jats:sec> <jats:title>Background.</jats:title> <jats:p>The aims of this study were to evaluate the efficacy of US Food and Drug Administration-approved drugs in genetically engineered pig-to-baboon kidney xenotransplantation and compare the results with those using an anti-CD40 monoclonal antibody (mAb)-based regimen.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods.</jats:title> <jats:p>Ten life-supporting kidney transplants were carried out in baboons using α1,3-galactosyltransferase gene-knockout/CD46 pigs with various other genetic manipulations aimed at controlling coagulation dysregulation. Eight transplants resulted in informative data. Immunosuppressive therapy consisted of induction with antithymocyte globulin and anti-CD20mAb, and maintenance based on either (1) CTLA4-Ig and/or tacrolimus (+rapamycin or mycophenolate mofetil) (<jats:italic toggle="yes">GroupA</jats:italic> [US Food and Drug Administration-approved regimens], n = 4) or (2) anti-CD40mAb + rapamycin (<jats:italic toggle="yes">GroupB</jats:italic>, n = 4). All baboons received corticosteroids, interleukin-6R blockade, and tumor necrosis factor-α blockade. Baboons were followed by clinical and laboratory monitoring of kidney function, coagulation, and immune parameters. At euthanasia, morphological and immunohistochemical studies were performed on the kidney grafts.</jats:p> </jats:sec> <jats:sec> <jats:title>Results.</jats:title> <jats:p>The median survival in <jats:italic toggle="yes">GroupB</jats:italic> was 186 days (range 90–260), which was significantly longer than in <jats:italic toggle="yes">GroupA</jats:italic>; median 14 days (range 12–32) (<jats:italic toggle="yes">P</jats:italic> &lt; 0.01). Only <jats:italic toggle="yes">GroupA</jats:italic> baboons developed consumptive coagulopathy and the histopathological features of thrombotic microangiopathic glomerulopathy and interstitial arterial vasculitis.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions.</jats:title> <jats:p>Recognizing that the pig donors in each group differed in some genetic modifications, these data indicate that maintenance immunosuppression including anti-CD40mAb may be important to prevent pig kidney graft failure.</jats:p> </jats:sec>