Beijing Tongren Hospital Capital Medical University
Experimental study on GTKO/CD46 Pig-to-Rhesus corneal xenotransplantation
Xiaojuan Dong1, Hidetaka Hara2, Ying Wang3, Yingnan Zhang1, Li Wang1, David K.C. Cooper2, Yifan Dai3, Zhiqiang Pan1.
1Ophthalmology, Beijing Tongren Hospital Capital Medical University, Beijing, People's Republic of China; 2Thomal E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, United States; 3Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, People's Republic of China
Purpose： Cornea blind can only be treated by allograft corneal transplantation. Since the serious shortage of donated corneas, many studies use pigs as the source animal for corneal xenotransplantation. Natural antibodies directed against α1,3-galactosyl -transferase(α1,3Gal) epitopes of pig organs are a major factor in xenograft rejection after transplantation into nonhuman primates, and antibodies directed against nonGal antigen is another factor. This study is to investigate the immunological characteristics of the recipients after GTKO/CD46 pig-to-rhesus corneal xenotransplantation.
Methods: Eight rhesus monkeys were divided into two groups. Group 1 use WT pigs as donors, group 2 use GTKO/CD46 pigs as donors, both groups use rhesus monkeys as recipients for corneal xenotransplantation. All rehsus monkeys underwent penetrating corneal xenotransplantation and received subconjunctival injections with betamethasone at 10 days interval for 5 times. All xenografts were evaluated by slit-lamp microscopy. A rejection index(RI) was based on the sum of the grades for opacity, edema and neovascularization. Grafts with scores ≥6 were considered to being rejection occurrence. T lymphocytes, B lymphocytes, and natural killer cells in peripheral blood were evaluated, plasma concentrations of pig red blood cell IgG/IgM antibodies were determined by flow cytometry.
Results： Anterior synechia occurred in two recipients in group 1 and all recipients in group 2. All recipients showed retro corneal membrane after xenotransplantation. Two recipients (have no anterior synechia) in group 1 showed xenografts rejection at 5 months and 3 months, two recipients (separate anterior synechia by second surgey) in group 2 showed xenografts rejection at 4 months and 6 months. Two recipients in both groups showed xenografts rejection in 1 month because of the anterior synechia. The plasma concentrations of WT pig red blood cell IgG/IgM antibodies showed a significant increase after surgery in group 1, the IgM antibodies showed an increase after surgery but the IgG antibodies showed no increase in group 2. The plasma concentrations of GTKO/CD46 pig red blood cell IgG/IgM antibodies showed no increased after surgery in group 1, the IgG antibodies showed a mild increase and the IgM antibodies showed no increase in group 2. CD4+ T lymphocytes, CD8+ T lymphocytes, CD20+ B lymphocytes and CD3-CD20-CD8+ NK cells in peripheral blood showed irregular fluctuations after surgery.
Conclusion： The corneal xenotransplantation using GTKO/CD46 pigs can prolong xenografts survival, but the risk of complication after surgery is similar with WT Pigs. Anterior synechia is the main reason of graft failure, retro corneal membrane might have effects on eyesight.
07:00 - 08:00
|Cell & Tissue Xenotransplantation: Tolerance||Experimental study on GTKO/CD46 Pig-to-Rhesus corneal xenotransplantation||Room 109|