Prevention of early loss of transplanted islets by targeting Na+/Ca2+exchanger of donor islets prior to transplantation

• Project/Area Number: 22390251
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Fukuoka University
• Principal Investigator: YASUNAMI Yohichi 福岡大学, 医学部, 教授 (00166521)
• Co-Investigator(Kenkyū-buntansha): IWAMOTO Takahiro 福岡大学, 医学部, 教授 (20300973)
• Co-Investigator(Renkei-kenkyūsha): TANIGUCHI Masaru 独立行政法人理化学研究所, 免疫制御研究グループ, グループディレクター (80110310)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2010: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
• Keywords: 移植外科学 / トランスポーター / 膵島移植 / NCX / 膵島細胞死 / 1型糖尿病 / 移植膵島障害

Research Abstract

A major obstacle facing clinical islet transplantation is the low efficiency of this procedure due to innate immune rejection of transplanted islets. In the present study, we demonstrate that the innate immune rejection of transplanted islets is triggered by injury of islet cells caused by Ca2+ influx into 〓 cells via Na+/Ca2+ exchanger (NCX) and that innate immune rejection can be prevented by the treatment of donor islets with NCX inhibitor prior to transplantation.

Research Products

• [Journal Article] Pretreatment of donor islets with the Na+/Ca2+ exchanger inhibitor improves the efficiency of islet transplantation. (2013)
  • Author(s): Mera T, Itoh T, Kita S, Kodama S, Kojima D, Nishinakamura H, Okamoto K, Ohkura M, Nakai J, Iyoda T, Iwamoto T, Matsuda T, Baba A, Omori K, Ono J, Watarai H, Taniguchi M, Yasunami Y.
  • Journal Title: Am J Transplant Volume: in press
  • Peer Reviewed
• [Journal Article] Prevention of High-Mobility Group Box 1-Mediated Early Loss of Transplanted Mouse Islets in the Liver by Antithrombin III. (2012)
  • Author(s): Kojima D, Mera T, Nishinakamura H, Itoh T, Ogata T, Matsuoka N, Kodama S, Yasunami Y.
  • Journal Title: Transplantation. Volume: 93(10) Pages: 983-8
  • Peer Reviewed
• [Journal Article] Prevention of High-Mobility Group Box 1-Mediated Early Loss of Transplanted Mouse Islets in the Liver by Antithrombin III. (2012)
  • Author(s): Kojima D, Mera T, Nishinakamura H, Itoh T, Ogata T, Matsuoka N, Kodama S, Yasunami Y.
  • Journal Title: Transplantation Volume: 93(10) Issue: 10 Pages: 983-8
  • DOI: 10.1097/tp.0b013e31824d3508
  • Peer Reviewed
• [Journal Article] Prevention of High-Mobility Group Box 1-Mediated Early Loss of Transplanted Mouse Islets in the Liver by Antithrombin III (2012)
  • Author(s): D Kojima, Y Yasunami, et al
  • Journal Title: Transplantation Volume: (In press)
  • Peer Reviewed
• [Journal Article] 糖尿病の新しい治療としての膵島細胞移植 (2011)
  • Author(s): 安波洋一
  • Journal Title: 九州実験動物雑誌 Volume: 27 Pages: 23-26
  • Peer Reviewed
• [Journal Article] 膵島移植とHMGB1 (2011)
  • Author(s): 安波洋一
  • Journal Title: バイオメヂカル Volume: 21 Pages: 42-46
  • Peer Reviewed
• [Journal Article] Assessment of islet quality following international shipping of more than 10,000 km. (2010)
  • Author(s): Ikemoto T, Matsumoto S, Itoh T, Noguchi H, Tamura Y, Jackson AM, Shimoda M, Naziruddin B, Onaca N, Yasunami Y, Levy MF.
  • Journal Title: Cell Transplant. Volume: VOL.19 Pages: 731-741
  • Peer Reviewed
• [Journal Article] Islet Transplantation Using Donors After Cardiac Death : Report of the Japan Islet Transplantation Registry (2010)
  • Author(s): Saito T, Gotoh M, Satomi S, Uemoto S, Kenmochi T, Itoh T, Kuroda Y, Yasunami Y, Matsumoto S, Teraoka S.
  • Journal Title: Transplantation Volume: VOL.90 Pages: 740-747
  • Peer Reviewed
• [Journal Article] Pretreatment of donor islets with the Na+/Ca2+ exchanger inhibitor improves the efficiency of islet transplantation.
  • Author(s): Mera T, Itoh T, Kita S, Kodama S, Kojima D, Nishinakamura H, Okamoto K, Ohkura M, Nakai J, Iyoda T, Iwamoto T, Matsuda T, Baba A, Omori K, Ono J, Watarai H, Taniguchi M, Yasunami Y.
  • Journal Title: Am J Transplant. Volume: (In press)
  • Peer Reviewed
• [Presentation] 単離ドナー膵島のNa+/Ca2+交換体を標的にした移植前治療による肝内移植早期膵島障害の新規制御法 (2013)
  • Author(s): 米良利之,伊東威,喜多紗斗美,小島大望,西中村瞳,永石美晴,小方貴子,金城亜哉,岩本隆宏,小玉正太,安波洋一
  • Organizer: 第40回日本膵・膵島移植研究会
  • Place of Presentation: 高松
  • Year and Date: 2013-03-02
• [Presentation] Inhibitory effect of thrombomodulin on HMGB1-stimulated IFN-γ production of hepatic NKT and Gr-1+ Cells, facilitating to prevent early loss of transplanted islets in the liver of mice. (2012)
  • Author(s): Kojima D, Nishinakamura H, Ogata T, Nagaishi M, Mera T, Itoh T, Matsuoka N, Kodama S, Yasunami Y.
  • Organizer: 24th International Congress of the Transplantation society
  • Place of Presentation: ドイツ、ベルリン
  • Year and Date: 2012-07-19
• [Presentation] トロンボモデュリンによる移植膵島早期膵島障害の制御 (2012)
  • Author(s): 小島大望、米良利之、西中村瞳、伊東威、松岡信秀、小玉正太、安波洋一
  • Organizer: 第39回日本膵・膵島移植研究会
  • Place of Presentation: 旭川
  • Year and Date: 2012-03-10
• [Presentation] 肝内移植早期膵島障害の機序と制御法 (2012)
  • Author(s): 安波洋一
  • Organizer: 第39回日本膵・膵島移植研究会
  • Place of Presentation: 旭川
  • Year and Date: 2012-03-09
• [Presentation] Inhibitory effect of thrombomodulin on HMGB1-stimulated IFN-γ production of hepatic NKT and Gr-1+ Cells, facilitating to prevent early loss of transplanted islets in the liver of mice. (2012)
  • Author(s): Kojima D, Nishinakamura H, Ogata T, Nagaishi M, Mera T, Itoh T, Matsuoka N, Kodama S, Yasunami Y.
  • Organizer: 24th International Congress of the Transplantation society
  • Place of Presentation: Berlin, Germany
• [Presentation] Targeting HMGB1 in Transplantation (2011)
  • Author(s): 安波洋一
  • Organizer: 3^<rd> HMGB1 International Worshop
  • Place of Presentation: Pittsburgh, USA(招待講演)
  • Year and Date: 2011-10-28
• [Presentation] 移植後24時間以内に発現する肝内移植膵島障害、喪失の機序解明と新規制御法開発 (2011)
  • Author(s): 米良利之、小島大望、西中村瞳、伊東威、松岡信秀、小玉正太、安波洋一
  • Organizer: 第38回日本膵・膵島移植研究会
  • Place of Presentation: 奈良
  • Year and Date: 2011-03-05
• [Presentation] 移植後24時間以内に発現する肝内移植膵島障害、喪失の機序解明と新規制御法開発 (2011)
  • Author(s): 米良利之、小島大望、西中村瞳、伊東威、松岡信秀、小玉正太、安波洋一
  • Organizer: 第38回日本膵・膵島移植研究会
  • Place of Presentation: 奈良県新公会堂(奈良)
  • Year and Date: 2011-03-05
• [Presentation] 高度医療としての膵島移植:今後の展開 (2011)
  • Author(s): 安波洋一
  • Organizer: 第45回糖尿病学の進歩
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2011-02-18
• [Presentation] Innate immunity in Transplantation (2011)
  • Author(s): 安波洋一
  • Organizer: The 2011 Fall Conference of the Korean Association of Immunologists
  • Place of Presentation: Seoul(招待講演)
• [Presentation] 門脈内移植膵島の自然免疫拒絶反応の制御 (2010)
  • Author(s): 安波洋一
  • Organizer: 第9回日本組織移植学会
  • Place of Presentation: コラッセふくしま(福島)
  • Year and Date: 2010-08-28
• [Presentation] High-mobility group box 1 is involved in the initial events of early loss of transplanted islets in mice. (2010)
  • Author(s): Nobuhide Matsuoka, Takeshi Itoh, Hiroshi Watarai, Etsuko Sekine-Kondo, Naoki Nagata, Kohji Okamoto, Toshiyuki Mera, Hiroshi Yamamoto, Shingo Yamada, Ikuro Maruyama, Masaru Taniguchi, Yohichi Yasunami
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-27
• [Presentation] Measuring of HMGB1 is a new useful potency assay to predict outcome of islet transplantation in mice. (2010)
  • Author(s): T Itoh, H Noguchi, M Takita, K Sugimoto, M Shimoda, B Naziruddin, MF Levy, Y Yasunami, S Matsumoto.
  • Organizer: XXIII International Congress of the Transplantation Society
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-18
• [Presentation] Actions of the Japanese Society for Pancreas and Islet Transplantation (JSPIT) for recipients of human islets isolated using Liberase HI (2010)
  • Author(s): T.Saito, M.Gotoh, S.Uemoto, T.Kenmochi, Y.Kuroda, Y.Yasunami, S.Satomi, T.Itoh, T.Kitamoto, S.Mohri, S.Teraoka
  • Organizer: XXIII International Congress of the Transplantation Society
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-16
• [Presentation] A Successful Pancreatic Islet Isolation in Cynomolgus Monkeys (2010)
  • Author(s): M.Ogura, M.Watanabe, Y.Koshizuka, D.Kuraya, T.Yoshida, K.Yamashita, H.Kamachi, T.Suzuki, M.Matsushita, Y.Yasunami, S.Todo
  • Organizer: XXIII International Congress of the Transplantation Society
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-16
• [Presentation] Early loss of transplanted islets in the liver of mice triggered by HMGBI is prevented by antithrombin III. (2010)
  • Author(s): D.Kojima, T.Mera, T.Itoh, N.Matsuoka, J.S.Kodama, Y.Yasunami
  • Organizer: XXIII International Congress of the Transplantation Society
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-16
• [Presentation] A novel approach to prevent early loss of transplanted islets by targeting donor islets with a PPARγ agonist prior to transplantation. (2010)
  • Author(s): T.Mera, D.Kojima, T.Itoh, N.Matsuoka, J.Ono, S.Kodama, Y.Yasunami
  • Organizer: XXIII International Congress of the Transplantati on Society
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2010-08-16
• [Presentation] Pancreatic islets contain abundant HMGB1 triggering early loss of transplanted islets in mice. (2010)
  • Author(s): Yohichi Yasunami
  • Organizer: 23rd Spring Congress of Korean Diabetes Association
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-05-07
• [Presentation] ドナー膵島のPPARγ agonistによる前処置は移植後膵島障害を軽減する (2010)
  • Author(s): 米良利之、小島大望、小玉正太、伊東威、新田智之、松岡信秀、中野昌彦、山下裕一、安波洋一
  • Organizer: 第110回日本外科学会定期学術集会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2010-04-09
• [Remarks] グローバルFUプログラムホームページ
  • URL: http://www.mcd.fukuoka-u.ac.jp/globalfu/
• [Patent(Industrial Property Rights)] NCXを標的とした単離膵島ならびに移植膵島障害の新規制御法 (2010)
  • Inventor(s): 安波洋一
  • Industrial Property Rights Holder: 福岡大学
  • Industrial Property Number: 2010-163146
  • Filing Date: 2010-07-20