Long-term survival of full-thickness corneal xenografts from α1,3-galactosyltransferase gene-knockout miniature pigs in non-human primates

Chang Ho Yoon, Se Hyun Choi, Hyuk Jin Choi, Hyun Ju Lee, Hee Jung Kang, Jong Min Kim, Chung Gyu Park, Kimyung Choi, Hyunil Kim, Curie Ahn, Mee Kum Kim

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Abstract

Background: We aimed to investigate (a) the long-term survival of corneal grafts from α1,3-galactosyltransferase gene-knockout miniature (GTKOm) pigs in non-human primates as a primary outcome and (b) the effect of anti-CD20 antibody on the survival of corneal grafts from GTKOm pigs as a secondary outcome. Methods: Nine rhesus macaques undergoing full-thickness corneal xenotransplantation using GTKOm pigs were systemically administered steroid, basiliximab, intravenous immunoglobulin, and tacrolimus with (CD20 group) or without (control group) anti-CD20 antibody. Results: Graft survival was significantly longer (P =.008) in the CD20 group (>375, >187, >187, >83 days) than control group (165, 91, 72, 55, 37 days). When we compared the graft survival time between older (>7- month-old) and younger (≤7-month-old) aged donor recipients, there was no significant difference. Activated B cells were lower in the CD20 group than control group (P =.026). Aqueous humor complement C3a was increased in the control group at last examination (P =.043) and was higher than that in the CD20 group (P =.014). Anti-αGal IgG/M levels were unchanged in both groups. At last examination, anti-non-Gal IgG was increased in the control group alone (P =.013). Conclusions: The GTKOm pig corneal graft achieved long-term survival when combined with anti-CD20 antibody treatment. Inhibition of activated B cells and complement is imperative even when using GTKO pig corneas.

Original languageEnglish
Article numbere12559
JournalXenotransplantation
Volume27
Issue number1
DOIs
StatePublished - 1 Jan 2020

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Keywords

  • anti-CD20 antibody
  • complement
  • cornea
  • non-Gal
  • non-human primate
  • xenotransplantation
  • α1,3-galactosyltransferase gene-knockout miniature (GTKOm) pig

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