Regulation of the delayed-type xenograft rejection and pig retrovirus

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390361
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Osaka University
• Principal Investigator: MIYAGAWA Syuji 大阪大学, 医学系・研究科, 准教授 (90273648)
• Co-Investigator(Renkei-kenkyūsha): NAGASHIMA Hiroshi 明治大学, 農学部生命科学科, 教授 (50318664) ; OKABE Masaru 大阪大学, 微生物病研究所, 教授 (30089875)
• Project Period (FY): 2009 – 2011
• Keywords: 糖鎖抗原 / レクチン・アレ / ブタ血管内皮 / PAI-2 / Dol-P-Mannosidase / N型糖鎖 / REPV

Research Abstract

For the purpose of the regulating the rejections in xenotransplantation, the carbohydrate antigens and the cellular factors was analyzed. In addition, porcine endogenous retrovirus was also studied.
1. The carbohydrate antigen of pig islets was compared with those of humans.
2. Pig CMAH gene was cloned, and the targeting vector was prepared.
3. Pig PAI-2 gene was cloned, and human modified-FasL gene was also established. The effect of the knockdown of the related gene to glycosylation on PERV was studied.

Research Products

• [Journal Article] Cloning of Homozygousα1, 3-Galactosyltransferase Gene Knock-Out Pigs Somatic Cell Nuclear Transfer (2012)
  • Author(s): Hitomi Matsunari, Masahito Watanabe, Kazuhiro Umeyama, Kazuaki Nakano, Yuka Ikezawa, Mayuko Kurome, Barbara Kessler, Eckhard Wolf, Shuji Miyagawa and Hiroshi Nagashima.
  • Journal Title: Open access Publisher INTECH Pages: 37-54
  • Peer Reviewed
• [Journal Article] Takehisa Ueno and Masahiro Fukuzawa Carbohydrate antigens (2012)
  • Author(s): Shuji Miyagawa, Yuichi Takama, Hiroshi Nagashima
  • Journal Title: Curr Opin Organ Transplant Volume: 17 Pages: 174-9
  • Peer Reviewed
• [Journal Article] A study of the glycoantigens of neonatal porcine islet-like cell clusters(NPCC) using a lectin microarray (2012)
  • Author(s): Shino Nakatsu, Yuichi Takama, Takehisa Ueno, Chikako Inuinaka, Shunsaku Takeishi, Akihiro Kondo, Teru Okitsu, Hiroshi Nagashima, Masahiro Fukuzawa and Shuji Miyagawa
  • Journal Title: Transplant Proc Volume: (In press)
• [Journal Article] A cloning of cytidine monophospho-N-acetylneuraminic acid(CMP-NeuAc) hydroxylase from porcine endothelial cell (2012)
  • Author(s): uke Ikeda, Aki Yamamoto, Akiko Nanjo, Chikako Inuinaka, Yuichi Takama, Takehisa Ueno, Masahiro Fukuzawa, Kazuaki Nakano, Hitomi Matsunari, Hiroshi Nagashima and Shuji Miyagawa.
  • Journal Title: Transplant Proc Volume: (In press)
  • Peer Reviewed
• [Journal Article] The blocking of CCR5 and CXCR3 suppresses the infiltration of macrophages in acute renal allograft rejection (2012)
  • Author(s): Yoichi Kakuta, Masayoshi Okumi, Shuji Miyagawa, Koichi Tsutahara, Toyofumi Abe, Koji Yazawa, Katsuyoshi Matsunami, Hideaki Otsuka, Shiro Takahara, Norio Nonomura.
  • Journal Title: Transplantation Volume: 93 Pages: 24-31
  • Peer Reviewed
• [Journal Article] Effects of a calcineurin inhibitor, FK506, and a CCR5/ CXCR3 antagonist, TAK-779, in a rat small intestinal transplantation model (2011)
  • Author(s): Yuichi Takama, Shuji Miyagawa, Aki Yamamoto, Sabere Firdawes, Takehisa Ueno, Yoshiyuki Ihara, Akihiro Kondo, Katsuyoshi Matsunami, Hideaki Otsuka, and Masahiro Fukuzawa.
  • Journal Title: Transplant Immunology Volume: 25 Pages: 49-55
  • Peer Reviewed
• [Journal Article] Expression of complement regulatory protein on porcine endogenous retrovirus(PERV) depends on molecular size (2010)
  • Author(s): Aki Yamamoto, Chizuko Kobayashi, Saya Yamashita, Takayuki Miyazawa, Masaru Okabe, Masahiro Fukuzawa, Shuji Miyagawa
  • Journal Title: Transplant Immunology Volume: 23 Pages: 71-6
  • Peer Reviewed
• [Journal Article] A Newly cloned pig dolichyl-phosphate mannosyltransferase for preventing the transmission of porcine endogenous retrovirus to human cells (2010)
  • Author(s): Aki Yamamoto, Shino Nakatsu, Akihiro Kondo, Tetsuya Asato, Masaru Okabe, Masahiro Fukuzawa, Shuji Miyagawa.
  • Journal Title: Transplant International Volume: 23 Pages: 424-31
  • Peer Reviewed
• [Journal Article] Survey of glycoantigens in cells from a1-3galactosyltransferase knockout pig using a lectin microarray (2010)
  • Author(s): Shuji Miyagawa, Shunsaku Takeishi, Aki Yamamoto, Kosuke Ikeda, Hitomi Matsunari, Masao Yamada, Masaru Okabe, Eiji Miyoshi, Masahiro Fukuzawa, Hiroshi Nagashima.
  • Journal Title: Xenotransplantation Volume: 17 Pages: 61-70
  • Peer Reviewed
• [Journal Article] Complement regulation in the GalT KO era (2010)
  • Author(s): Shuji Miyagawa, Aki Yamamoto, Katsuyoshi Matsunami, Dandan Wang, Yuichi Takama, Takehisa Ueno, Masaru Okabe, Hiroshi Nagashima, Masahiro Fukuzawa.
  • Journal Title: Xenotransplantation Volume: 17 Pages: 11-25
  • Peer Reviewed
• [Journal Article] Construction of the Plasmid, Overexpression by Chinese Hamster Ovary Cell, Purification, and Characterization of the First Three Short Consensus Repeat Modules of Human Complement Receptor Type 1 (2009)
  • Author(s): Atsushi Yamaguchi, Hiroaki Takagawa, Hirofumi Iwakaji, Shuji Miyagawa, Pi-Chao Wang, and Noriyuki Ishii.
  • Journal Title: J B Volume: 145 Pages: 533-42
  • Peer Reviewed
• [Journal Article] Successful Treatment of Cardiogenic Shock Caused by Humoral Cardiac Allograft Rejecti (2009)
  • Author(s): Saito S, Matsumiya G, Fukushima N, Sakaguchi T, Fujita T, Ueno T, Miyagawa S, Yamauchi A, Sawa Y.
  • Journal Title: Circ J Volume: 73 Pages: 970-3
  • Peer Reviewed
• [Presentation] ブタ膵島の糖鎖抗原について (2012)
  • Author(s): 王丹丹、高間勇一、上野豪久、福沢正洋、宮川周士、(東京大学)興津輝、(米ベイラー大)松本慎一、(東北大学)後藤昌史、(明治大学)長嶋比呂志
  • Organizer: 第39回膵・膵島移植研究会
  • Place of Presentation: 旭川医大
  • Year and Date: 20120309-10
• [Presentation] バイオ人工細胞・臓器の世界の現況 (2012)
  • Author(s): 宮川周士
  • Organizer: 第2回公開シンポジウム・先進医用ブタの開発と前臨床研究拠点形成プロジェクト
  • Place of Presentation: 鹿児島大学
  • Year and Date: 2012-03-22
• [Presentation] In comparison with APIs, NICCs are very rich in a2, 6Neu5NAc, and reduced Fucose/ Core Fucose & high-mannose form, and Lactosamine & Core 1 forms are upregulated, instead, in 5 day cultures (2011)
  • Author(s): Hiroaki Kashiwada, Akiko Nanjyo, Shino Nakatsu, Yuichi Takama, Teru Okitsu, Hiroshi Nagashima, Masahiro Fukuzawa, Shuji Miyagawa. P
  • Organizer: The 11th Congress of International Congress for Xenotransplantation(Joint Conference with CST)
  • Place of Presentation: Miami, USA
  • Year and Date: 20111023-26
• [Presentation] αGal-knockoutブタ関連の膵島の糖鎖抗原の解析 (2011)
  • Author(s): 宮川周士、南條明子、柏田紘明、福沢正洋、武石俊作、興津輝、(明治大学・農学部)長嶋比呂志、(米ベイラー大)松本慎一
  • Organizer: 第47回日本移植学会
  • Place of Presentation: 福島県立医大
  • Year and Date: 20111005-06
• [Presentation] ブタCMAH遺伝子制御による抗原性の変化の検討 (2011)
  • Author(s): 高間勇一、柏田紘明、南條明子、中津志野、王丹丹、福沢正洋、宮川周士、(明治大学・農学部)長嶋比呂志
  • Organizer: 第47回日本移植学会
  • Place of Presentation: 福島県立医大
  • Year and Date: 20111005-06
• [Presentation] study of the glycoantigens of neonatal porcine islet-like cell clusters using a lectin microarray (2011)
  • Author(s): Hiroaki Kashiwada, Akiko Nanjyo, Shino Nakatsu, Shunsaku Takeishi, Yuichi Takama, Akihiro Kondo, Teru Okitsu, Hiroshi Nagashima, Masahiro Fukuzawa, Shuji Miyagawa P
  • Organizer: 2th Congress of the Asian Society of Transplantation
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20110925-28
• [Presentation] Trial of knockdown for the H-D antigen of pig cells (2011)
  • Author(s): Akiko Nanjyo, Aki Yamamoto, Hiroaki Kashiwada, Kosuke Ikeda, Yuichi Takama, Takehisa Ueno, Masahiro Fukuzawa, Akihiro Kondo, Hiroshi Nagashima, Shuji Miyagawa P
  • Organizer: 12th Congress of the Asian Society of Transplantation
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20110925-28
• [Presentation] A cloning of cytidine monophospho-N-acetylneuraminic acid(CMP-NeuAc) hydroxylase from porcine endothelial cells (2011)
  • Author(s): Kosuke Ikeda, Akiko Nanjyo, Hiroaki Kashiwada, Yuichi Takama, Takehisa Ueno, Masahiro Fukuzawa, Kazuaki Nakano, Hitomi Matsunari, Hiroshi Nagashima, Shuji Miyagawa P
  • Organizer: 12th Congress of the Asian Society of Transplantation
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20110925-28
• [Presentation] (Invited) Complements in transplantation (2011)
  • Author(s): Shuji Miyagawa O
  • Organizer: 12th Congress of the Asian Society of Transplantation
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20110925-28
• [Presentation] Effects of a calcineurin inhibitor, FK506, and a CCR5/ CXCR3 antagonist, TAK-779, in a rat small intestinal transplantation model (2011)
  • Author(s): Yuichi Takama, Shuji Miyagawa, Takehisa Ueno, Masahiro Fukuzawa O
  • Organizer: XIIth International Small Bowel Transplant Symposium
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20110915-18
• [Presentation] 異種移植ブタ開発研究の流れ (2011)
  • Author(s): 宮川周士・王丹丹・高間勇一・上野豪久・福沢正洋、長嶋比呂志
  • Organizer: 第14回日本異種移植研究会
  • Place of Presentation: 広島大学
  • Year and Date: 2011-12-10
• [Presentation] αGal-knockoutブタ関連の膵島の糖鎖抗原の解析 (2011)
  • Author(s): 王丹丹、高間勇一、上野豪久、武石俊作、福沢正洋、宮川周士、(東京大学・生産技術研究所)興津輝、(米ベイラー大)松本慎一、(明治大学・農学部)中野和明、松成ひとみ、長嶋比呂志
  • Organizer: 第14回日本異種移植研究会
  • Place of Presentation: 広島大学
  • Year and Date: 2011-12-10
• [Presentation] 新生児ブタ膵島の糖鎖について (2011)
  • Author(s): 王丹丹、高間勇一、上野豪久、南條明子、乾中智佳子、福沢正洋、武石俊作、宮川周士、(東京大学・生産技術研究所)興津輝、(明治大学・農学部)長嶋比呂志
  • Organizer: 第14回日本異種移植研究会
  • Place of Presentation: 広島大学
  • Year and Date: 2011-12-10
• [Presentation] ラット小腸移植におけるケモカイン阻害剤及びカルシニューリン阻害剤の効果の検討 (2011)
  • Author(s): 高間勇一, 宮川周士, 山本亜紀, 井原欣幸, 上野豪久, 福澤正洋
  • Organizer: 第23回小腸移植研究会
  • Place of Presentation: 熊本大学
  • Year and Date: 2011-03-11
• [Presentation] Multilateral inhibition of complement activation in the GalT KO era (2010)
  • Author(s): Shuji Miyagawa, Dandan Wang, Yuichi Takama, Masahiro Fukuzawa
  • Organizer: Korean Society for Transplantation(40th)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20101112-13
• [Presentation] Effects of a calcineurin inhibitor, FK506, and a CCR5/ CXCR3 antagonist, TAK-779, in a rat small intestinal transplantation model (2010)
  • Author(s): Takama Y, Miyagawa S, Firdawes S, Ueno T, Yamamoto A, Wang D, Ikeda K, Fukuzawa M. P
  • Organizer: The XXIII International Congress of Transplantation
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20100815-19
• [Presentation] An analysis of pig cytidine monophospho-N-acetylneuraminic acid(CMP-NeuAc) hydroxylase (2010)
  • Author(s): Kosuke Ikeda, Aki Yamamoto, Akihiro Kondo, Yuichi Takama, Masahiro Fukuzawa, Hitomi Matsunari, Hiroshi Nagashima, Shuji Miyagawa Mini O
  • Organizer: The XXIII International Congress of Transplantation
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20100815-19
• [Presentation] A study of the Prevention of PERV Infection by siRNA on Pig Dolichyl-Phosphate Mannosyltransferase (2010)
  • Author(s): Aki Yamamoto, Akihiro Kondo, Shino Nakatsu, Kosuke Ikeda, Sabere Firdawes, Dandan Wang, Yuichi Takama, Takehisa Ueno, Masahiro Fukuzawa, Shuji Miyagawa O
  • Organizer: The XXIII International Congress of Transplantation
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 20100815-19
• [Presentation] αGal-knockoutブタ膵島(NICC)の糖鎖抗原の解析 (2010)
  • Author(s): 山本亜紀、池田孔佑、松成ひとみ、長嶋比呂志、武石俊作、山田正雄、高間勇一、福澤正洋、宮川周士
  • Organizer: 第37回膵・膵島移植研究会
  • Place of Presentation: 独協大学
  • Year and Date: 20100312-13
• [Presentation] Complement activation on the xeno-cells Seoul Forum on Xenotransplantation (2010)
  • Author(s): Shuji Miyagawa
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-11-10
• [Presentation] レクチンブロット法によるαGal-knockoutブタ膵島の糖鎖抗原の解析 (2010)
  • Author(s): 宮川周士、山本亜紀、興津輝、長嶋比呂志、高間勇一、井原欣幸、上野豪久、福澤正洋
  • Organizer: 第46回日本移植研究会
  • Place of Presentation: 京都府立医大
  • Year and Date: 2010-10-21
• [Presentation] ブタCMAH遺伝子ノックダウンによる抗原性の検討 (2010)
  • Author(s): (王丹丹, )山本亜紀, 池田孔佑, 長嶋比呂志, 高間勇一, 上野豪久, 井原欣幸, 福澤正洋, 宮川周士
  • Organizer: 第46回日本移植研究会
  • Place of Presentation: 京都府立医大
  • Year and Date: 2010-10-21
• [Presentation] ラット小腸移植におけるケモカイン阻害剤TAK-779及びカルシニューリン阻害剤FK506の効果の検討 (2010)
  • Author(s): 高間勇一, 宮川周士, フルダウス・サビエル, 山本亜紀, 井原欣幸, 上野豪久, 福澤正洋
  • Organizer: 第46回日本移植研究会
  • Place of Presentation: 京都府立医大
  • Year and Date: 2010-10-21
• [Presentation] ラット小腸移植におけるケモカイン阻害剤及びカルシニューリン阻害剤の効果の検討 (2010)
  • Author(s): 高間勇一, 宮川周士, フルダウス・サビエル, 山本亜紀, 池田孔佑, 上野豪久, 福澤正洋
  • Organizer: 第47回日本小児外科学会
  • Place of Presentation: 名古屋保健衛生大学
  • Year and Date: 2010-06-17
• [Presentation] ブタDolichyl-phosphate mannosyltransferase(DPM) knockdownによるブタ内在性レトロウイルス(PERV)の感染制御 (2010)
  • Author(s): 山本亜紀, 中津志野, 近藤昭宏, 池田孔佑、間勇一, 上野豪久, 福澤正洋, 宮川周士
  • Organizer: 第13回日本異種移植研究会
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2010-03-14
• [Presentation] ブタCMP-N-acetylneuraminic acid hydroxylase geneの解析 (2010)
  • Author(s): 池田孔佑、山本亜紀、近藤昭宏、松成ひとみ、長嶋比呂志、高間勇一, 上野豪久, 福澤正洋、宮川周士
  • Organizer: 第13回日本異種移植研究会
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2010-03-14
• [Presentation] α1, 3ガラクトース転移酵素遺伝子ダブルノックアウトブタの体細胞クローニングにおけるScriptaidの効果 (2010)
  • Author(s): 松成ひとみ、池澤有加、渡邊将人、梅山大、中野和明、藤原主、竹内靖浩、本田香澄、前原美樹、高柳就子、山田和彦、宮川周士、長嶋比呂志
  • Organizer: 第13回日本異種移植研究会
  • Place of Presentation: 東京医科歯科大学
  • Year and Date: 2010-03-14
• [Presentation] ラット小腸移植におけるケモカイン阻害剤及びカルシニューリン阻害剤の効果の検討 (2010)
  • Author(s): 高間勇一、宮川周士、フルダウスサビエル、山本亜紀、池田孔佑、上野豪久、福沢正洋
  • Organizer: 第22回小腸移植研究会
  • Place of Presentation: 慶応義塾大学
  • Year and Date: 2010-03-06
• [Presentation] Expression of Complement Regulatory Protein on Porcine Endogenous Retrovirus depends on Molecular Size (2009)
  • Author(s): Aki Yamamoto, Chizuko Kobayashi, Saya Yamashita, Kosuke Ikeda, Masahiro Fukuzawa, Shuji Miyagawa O
  • Organizer: The 10th Congress of International Congress for Xenotransplantation(Joint Conference with IPITA)
  • Place of Presentation: Venice, Italy
  • Year and Date: 20091012-16
• [Presentation] Lectin microarray analyses of endothelial cells and fibroblasts from the a1, 3 galactosyltransferase knockout pig (2009)
  • Author(s): Shuji Miyagawa, Aki Yamamoto, Kosuke Ikeda, Hitomi Matsunari, Hiroshi Nagashima, Shunsaku Takeishi, Masao Yamada, Eiji Miyoshi, Masahiro Fukuzawa O
  • Organizer: pig. The 10th Congress of International Congress for Xenotransplantation(Joint Conference with IPITA),
  • Place of Presentation: Venice, Italy
  • Year and Date: 20091012-16
• [Presentation] Complement regulation in the GalT KO era (2009)
  • Author(s): Shuji Miyagawa Plenary
  • Organizer: The 10th Congress of International Congress for Xenotransplantation(Joint Conference with IPITA)
  • Place of Presentation: Venice, Italy
  • Year and Date: 20091012-16
• [Presentation] レクチンブロット法によるαGal-knockoutブタの糖鎖抗原の解析 (2009)
  • Author(s): 山本亜紀、徐恒傑、武石俊作、山田正雄、三善英知、池田孔佑、松成ひとみ、長嶋比呂志、福澤正洋、宮川周士
  • Organizer: 第44回日本移植学会
  • Place of Presentation: 東京女子医大
  • Year and Date: 20090916-18
• [Presentation] ブタCMP-N-acetylneuraminic acid hydroxylase geneの解析 (2009)
  • Author(s): 池田孔佑、山本亜紀、松成ひとみ、中野和明、藤原主、長嶋比呂志、福澤正洋、宮川周士
  • Organizer: 第44回日本移植学会
  • Place of Presentation: 東京女子医大
  • Year and Date: 20090916-18
• [Presentation] ラット小腸移植におけるケモカイン阻害剤及びカルシニューリン阻害剤の効果の検討 (2009)
  • Author(s): 高間勇一、宮川周士、徐恒傑、フルダウス・サビエル、山本亜紀、池田孔佑、上野豪久、福沢正洋
  • Organizer: 第44回日本移植学会
  • Place of Presentation: 東京女子医大
  • Year and Date: 20090916-18
• [Presentation] Effects of a calcineurin inhibitor, FK506, and a CCR5/ CXCR3 antagonist, TAK-779, in a rat small intestinal transplantation model (2009)
  • Author(s): Takama Y, Miyagawa S, Xu H, Ueno T, Firdawes S, Yamamoto A, Ikeda K, Fukuzawa M. P
  • Organizer: XIth International Small Bowel Transplant Symposium
  • Place of Presentation: Bologna, Italy
  • Year and Date: 20090909-12
• [Presentation] Profiles of xeno-glycoantigens of the cell from a1, 3 galactosyltransferase knockout pig (2009)
  • Author(s): Shuji Miyagawa, Shunsaku Takeishi, Aki Yamamoto, Kosuke Ikeda, Hitomi Matsunari, Hiroshi Nagashima, Masao Yamada, Eiji Miyoshi, Masahiro Fukuzawa
  • Organizer: Joint Conference of CTS(10^<th> biannual) & JSOPMB(36^<th> annul)
  • Place of Presentation: Okayama
  • Year and Date: 20090420-21
• [Book] Xenotransplantation (2012)
  • Author(s): Shuji Miyagawa
  • Total Pages: 37-54
  • Publisher: INTECH
• [Remarks]
  • URL: http://www.med.osaka-u.ac.jp/pub/orgtrp/www/index-jp.html