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Presenter: Hisashi, Sahara, Kagoshima, Japan
Authors: Hisashi Sahara1, Hiroshi Nagashima2, Mitsuhiro Sekijima1, Masayuki Tasaki1, Kentaro Setoyama1, Hitomi Matsunari2, Kazuaki Nakano2, Hiroshi Date3, Akira Shimizu1, Kazuhiko Yamada1
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Prevention of hyper-acute pulmonary xenograft dysfunction using GalT-KO swine in an ex-vivo lung perfusion model
Hisashi Sahara1, Hiroshi Nagashima2, Mitsuhiro Sekijima1, Masayuki Tasaki1, Kentaro Setoyama1, Hitomi Matsunari2, Kazuaki Nakano2, Hiroshi Date3, Akira Shimizu1, Kazuhiko Yamada1
1Xenotransplantation Surgery Section, Frontier Science Research Center, Kagoshima University, Kagoshima; 2Laboratory of Developmental Engineering, Department of Life Sciences, Meiji University, School of Agriculture, Kanagawa; 3Department of Thoracic Surgery, Kyoto University, Kyoto; Japan
Background: The results of both heart and kidney GalT-KO swine-to-primate studies have been more encouraging than for lung xenotransplantation models. This may be because research in pulmonary xenotransplantation is limited. Here, we evaluated whether GalT-KO lungs could prevent hyper-acute pulmonary xenograft dysfunction using ex-vivo lung perfusion model.
Methods: Porcine heart-lung blocks were procured from wild-type (WT) and GalT-KO swine generated at Meiji University. In group 1 (n=2), WT lungs were perfused with autologous blood to obtain baseline values of pulmonary physiology using this system. Then, either WT (group 2: n=2) or GalT-KO (group 3: n=2) lungs were perfused with human blood for 120 minutes. Changes in pulmonary arterial pressure, pulmonary vascular resistance (PVR), gas exchange, complete blood counts and other key variables were followed serially. Following perfusion, the graft tissue was evaluated histologically.
Results: WT lungs perfused with autologous blood displayed normal pulmonary function with only 25% increase of PVR (group 1). Perfusion of human blood through WT porcine lungs led to 100% increase of PVR within 60 minutes (group 2). In contrast, GalT-KO porcine lungs with human blood demonstrated nearly stable function for 120 minutes with only 30% increase of PVR (group 3). After 60 minutes of perfusion, platelets counts within the perfusate decreased to 14% of pre-perfusion levels in group 2, compared with 50% in group 3. Immunohistochemistry revealed limited IgM and complement deposition in group 3 and confirmed this GalT-KO swine did not express Gal antigen using IB4 staining.
Conclusion: GalT-KO lungs exhibited stable pulmonary function compared with WT lungs when perfused with human blood in a clinically relevant ex-vivo perfusion model. Further studies are required in order to understand better the mechanisms of pulmonary xenograft rejection and dysfunction.
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