{"created":"2023-07-25T08:08:20.515214+00:00","id":7697,"links":{},"metadata":{"_buckets":{"deposit":"539d7ef7-7135-438f-bad6-95c95cfbffaf"},"_deposit":{"created_by":3,"id":"7697","owners":[3],"pid":{"revision_id":0,"type":"depid","value":"7697"},"status":"published"},"_oai":{"id":"oai:ir.kagoshima-u.ac.jp:00007697","sets":["31:160:161"]},"author_link":["36768","112114","112113"],"item_8_alternative_title_18":{"attribute_name":"別言語のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"GalT-knockout pig to monkey xenogeneic kidney and islet transplantation"}]},"item_8_alternative_title_19":{"attribute_name":"タイトルよみ","attribute_value_mlt":[{"subitem_alternative_title":"シンライセイ ノ カクリツ シタ Gal カンゼン ノックアウト ブタ オ モチイタ ブタ・サル カン イシュ ジン・スイトウ イショク"}]},"item_8_date_6":{"attribute_name":"作成日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2011-03-31"}]},"item_8_description_4":{"attribute_name":"要約(Abstract)","attribute_value_mlt":[{"subitem_description":"2007-2010年度科学研究費補助金(基盤研究(A))研究成果報告書 課題番号:19209043 研究代表者:山田和彦 (鹿児島大学フロンティアサイエンス研究推進センター教授)","subitem_description_type":"Other"},{"subitem_description":"移植医療が定着する欧米でも臓器不足は大きな問題であり、医用動物臓器をドナーに用いる異種移植は有力な解決策である。前臨床研究としてブタをドナーとしたサルへの異種移植を行い、(1)Galノックアウト(KO)MHC確立ミニブタ細胞核を用いた核移植による国内でのGalKOブタ作出、(2)国内作出GalKOブタ腎のサルへの国内初の移植で15日間拒絶が皆無、(3)当研究室確立の新規免疫抑制療法で、国内初となる異種間膵島移植での2カ月間正常血糖維持という成果を得た。更に、(4)RIを用いない移植後細胞性免疫反応評価法の確立、(5)ヒトCD47による、異種間マクロファージ貪食作用抑制とT細胞反応軽減、(6)Non-Gal抗原に対するAccommodation成立に対するCD59関与の示唆という結果を得た。","subitem_description_type":"Other"},{"subitem_description":"Due largely to improvements in immunosuppressive therapies, organ transplantation has become the primary cure for end-stage organ failure in the United States, Europe, as well as Japan. However, the current shortage of donor organs is a critical problem. One attractive solution is xenotransplantation utilizing miniature swine donor organs. However, because human blood contains native antibodies (NAb) directed toward a constitutively expressed pig cell surface carbohydrate called galactose-alpha-1,3-galactose (Gal), pig-to-human xenotransplantation initially resulted in hyper-acute (graft loss in < 1day) humoral rejection. With this grant support in the past four years, we have made two major achievements, neither of which had previously been accomplished in Japan. Achievement 1 (first domestic success): Using nuclear transfer from somatic nuclei of GalT-KO miniature swine, obtained from the TBRC at Harvard Medical School, we and our colleagues, as a collaborative effort, succeeded in producing GalT-KO miniature swine. We then transplanted GalT-KO kidneys from those pigs into cynomologous monkeys to confirm that hyperacute rejection was avoidable. Rejection did not occur for 15 days after xenotransplantation. Achievement 2 (first domestic success): We successfully isolated islets from miniature swine and, following xenogeneic transplantation of these islets, we observed maintenance of normal blood glucose levels up to two months in monkeys. In addition, we have explored the mechanisms of rejection in xenotransplantation. In particular, our results utilizing GalT-KO swine suggested that CD59 is involved in development of accommodation. Moreover, our studies have suggested immune-regulatory/protective effects by (1) transgene human CD47 onto porcine cells and (2) administration of soluble thrombomodulin or hepatocyte growth factor. Using the support of this grant, we have developed new immunosuppressive regimens for renal/islet xenotransplantation, including these reagents.","subitem_description_type":"Other"}]},"item_8_full_name_2":{"attribute_name":"著者よみ","attribute_value_mlt":[{"nameIdentifiers":[{}],"names":[{"name":"ヤマダ, カズヒコ"}]}]},"item_8_full_name_3":{"attribute_name":"別言語の著者","attribute_value_mlt":[{"nameIdentifiers":[{}],"names":[{"name":"YAMADA, Kazuhiko"}]}]},"item_8_publisher_23":{"attribute_name":"公開者・出版者","attribute_value_mlt":[{"subitem_publisher":"鹿児島大学"}]},"item_8_subject_15":{"attribute_name":"NDC","attribute_value_mlt":[{"subitem_subject":"494","subitem_subject_scheme":"NDC"}]},"item_8_text_24":{"attribute_name":"公開者よみ","attribute_value_mlt":[{"subitem_text_value":"カゴシマ ダイガク"}]},"item_8_text_25":{"attribute_name":"公開者別名","attribute_value_mlt":[{"subitem_text_value":"Kagoshima University"}]},"item_8_text_41":{"attribute_name":"科研費番号 ","attribute_value_mlt":[{"subitem_text_value":"19209043"}]},"item_8_version_type_14":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"山田, 和彦"}],"nameIdentifiers":[{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2016-10-28"}],"displaytype":"detail","filename":"19209043seika.pdf","filesize":[{"value":"246.6 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"19209043seika.pdf","url":"https://ir.kagoshima-u.ac.jp/record/7697/files/19209043seika.pdf"},"version_id":"b9530f53-7f51-48f0-8638-5c8e15572f77"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"異種移植","subitem_subject_scheme":"Other"},{"subitem_subject":"ブタ・サル間移植","subitem_subject_scheme":"Other"},{"subitem_subject":"腎移植","subitem_subject_scheme":"Other"},{"subitem_subject":"膵島移植","subitem_subject_scheme":"Other"},{"subitem_subject":"GalKOブタ","subitem_subject_scheme":"Other"},{"subitem_subject":"遺伝子導入","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"信頼性の確立したGal完全ノックアウトブタを用いたブタ・サル間異種腎・膵島移植","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"信頼性の確立したGal完全ノックアウトブタを用いたブタ・サル間異種腎・膵島移植"}]},"item_type_id":"8","owner":"3","path":["161"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-01-06"},"publish_date":"2015-01-06","publish_status":"0","recid":"7697","relation_version_is_last":true,"title":["信頼性の確立したGal完全ノックアウトブタを用いたブタ・サル間異種腎・膵島移植"],"weko_creator_id":"3","weko_shared_id":3},"updated":"2023-09-01T10:38:37.495798+00:00"}