Establishment of minimally invasive cell therapy for diabetes by improving the outcome of pancreatic islet transplantation

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390337
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: Tohoku University
• Principal Investigator: GOTO Masafumi 東北大学, 未来科学技術共同研究センター, 教授 (50400453)
• Co-Investigator(Kenkyū-buntansha): SATOMI Susumu 東北大学, 病院, 教授 (00154120) ; HINOKIO Yoshinori 東北大学, 大学院・医学系研究科, 非常勤講師 (10282071)
• Co-Investigator(Renkei-kenkyūsha): OKADA Hidechika 名古屋市立大学, 大学院・医学研究科, 名誉教授 (30160683) ; MANO Yoshihiro 東京医科歯科大学, 大学院・保健衛生学研究科, 名誉教授 (70014339)
• Project Period (FY): 2008 – 2010
• Keywords: 移植・再生医療 / 糖尿病 / 細胞・組織 / 膵島

Research Abstract

In the present study, we have clarified that brain death in combination with warm ischemic stress during isolation procedures induces a high expression of inflammatory mediators in isolated islets. We also found that C5a inhibitory peptide attenuates cross-talk between the complement and coagulation cascades through suppressing up-regulation of tissue factor expression on leukocytes in recipient livers, a process leading to improvement in islet engraftment. This was a new concept to improve the outcome of islet transplantation. We also showed that isoflurane and short-term fasting combined with insulin treatment could be a promising regimen for improving islet engraftment in the liver.

Research Products

• [Journal Article] Quantification of the islet product : Presentation of a standardized current Good Manufacturing Practices compliant system with minimal variability (2011)
  • Author(s): Friberg A, Brandhorst H, Buchwald P, Goto M, Ricordi C, Brandhorst D, Korsgren O
  • Journal Title: Transplantation Volume: 91 Pages: 677-683
  • Peer Reviewed
• [Journal Article] 膵島移植の現状と課題 (2011)
  • Author(s): 後藤昌史
  • Journal Title: 総合臨床 Volume: (in press)
  • Peer Reviewed
• [Journal Article] C5a阻害による補体系・凝固系のcross-talkの抑制を介した移植後早期膵島障害の制御 (2011)
  • Author(s): 戸子台和哲、後藤昌史、稲垣明子、中西渉、小川則彦、佐藤和重、川岸直樹、関口悟、Bo Nilsson、岡田則子、岡田秀親、里見進
  • Journal Title: 移植 Volume: (in press)
  • Peer Reviewed
• [Journal Article] 膵島移植の現状 (2011)
  • Author(s): 後藤昌史
  • Journal Title: 臨床医のための循環器診療 Volume: (in press)
  • Peer Reviewed
• [Journal Article] 吸入麻酔イソフルランが膵島移植に及ぼす影響 (2011)
  • Author(s): 山谷英之、後藤昌史、Feng Zhaoqiang、猪村武弘、小林英司、里見進
  • Journal Title: 移植 Volume: (in press)
  • Peer Reviewed
• [Journal Article] MRIを用いた移植膵島の生着評価法 (2011)
  • Author(s): 坂田直昭、後藤昌史、江川新一、海野倫明
  • Journal Title: 膵臓 Volume: (in press)
  • Peer Reviewed
• [Journal Article] Attenuation of cross-talk between the complement and coagulation cascades by C5a blockade improves early outcomes after intraportal islet transplantation (2010)
  • Author(s): Tokodai K, Goto M, Inagaki A, Nakanishi W, Ogawa N, Satoh K, Kawagishi N, Sekiguchi S, Nilsson B, Okada N, Okada H, Satomi S
  • Journal Title: Transplantation Volume: 90(12) Pages: 1358-1365
  • Peer Reviewed
• [Journal Article] The impact of ischemic stress on the quality of isolated pancreatic islets (2010)
  • Author(s): Goto M, Imura T, Inagaki A, Ogawa N, Yamaya H, Fujimori K, Kurokawa Y, Satomi S
  • Journal Title: Transplantation Proc Volume: 42(6) Pages: 2040-2042
  • Peer Reviewed
• [Journal Article] C5a-Inhibitory peptide combined with gabexate mesilate prevents the Instant Blood-Mediated Inflammatory Reaction in a rat model of islet transplantation (2010)
  • Author(s): Tokodai K, Goto M, Inagaki A, Nakanishi W, Okada N, Okada H, Satomi S
  • Journal Title: Transplantation Proc Volume: 42(6) Pages: 2102-2103
  • Peer Reviewed
• [Journal Article] Brain death in combination with warm ischemic stress during isolation procedures induces the expression of crucial inflammatory mediators in the isolated islets (2010)
  • Author(s): Saito Y, Goto M, Maya K, Ogawa N, Fujimori K, Kurokawa Y, Satomi S
  • Journal Title: Cell Transplantation Volume: 19(6) Pages: 775-782
  • Peer Reviewed
• [Journal Article] ここまで進んだ膵島移植 (2010)
  • Author(s): 後藤昌史
  • Journal Title: 糖尿病診療マスター Volume: 8(2) Pages: 203-207
  • Peer Reviewed
• [Journal Article] A novel predictive method for assesing the quality of isolated pancreatic islets using a scanning electrochemical microscopy (2009)
  • Author(s): Goto M, Abe H, Ito-Sasaki T, Goto M, Inagaki A, Ogawa N, Fujimori K, Kurokawa Y, Matsue T, Satomi S
  • Journal Title: Transplantation Proc Volume: 41(1) Pages: 311-313
  • Peer Reviewed
• [Journal Article] The influence of brain death on tissue factor expression in the pancreatic tissues and isolated islets in rats (2009)
  • Author(s): Saito Y, Goto M, Maya K, Ogawa N, Fujimori K, Kurokawa Y, Satomi S
  • Journal Title: Transplantation Proc Volume: 41(1) Pages: 307-310
  • Peer Reviewed
• [Journal Article] Superiority of fresh islets compared with cultured islets (2009)
  • Author(s): Takahashi H, Goto M, Ogawa N, Saito Y, Fujimori K, Kurokawa Y, Doi H, Satomi S
  • Journal Title: Transplantation Proc Volume: 41(1) Pages: 350-351
  • Peer Reviewed
• [Journal Article] C5a inhibitory peptide combined with gabexate mesilate is a clinically available candidate for preventing the instant blood-mediated inflammatory reaction (2009)
  • Author(s): Tokodai K, Goto M, Imura T, Ogawa N, Fujimori K, Kurokawa Y, Okada H, Satomi S
  • Journal Title: Transplantation Proc Volume: 41(1) Pages: 67-68
  • Peer Reviewed
• [Journal Article] How Much of the Pancreatic Head Should We Resect in Frey's Procedure? (2009)
  • Author(s): Sakata N, Egawa S, Motoi F, Goto M, Matsuno S, Katayose Y, Unno M
  • Journal Title: Surg Today Volume: 39 Pages: 120-127
  • Peer Reviewed
• [Journal Article] ラット膵島移植モデルにおける移植前培養膵島に対する新鮮膵島の優位性の検証 (2009)
  • Author(s): 高橋英幸、後藤昌史、小川則彦、藤盛啓成、黒川良望、土井秀之、里見進
  • Journal Title: 移植 Volume: 44(1) Pages: 82-90
  • Peer Reviewed
• [Journal Article] 膵島移植の現状と展望 (2009)
  • Author(s): 後藤昌史
  • Journal Title: 最新医学 Volume: 64(2) Pages: 45-52
  • Peer Reviewed
• [Journal Article] Dissecting the instant blood-mediated inflammatory reaction in islet xenotransplantation (2008)
  • Author(s): Goto M, Tjernberg J, Dufrane D, Elgue G, Brandhorst D, Ekdahl KN, Brandhorst H, Wennberg L, Kurokawa Y, Satomi S, Lambris JD, Gianello P, Korsgren O, Nilsson B
  • Journal Title: Xenotransplantation Volume: 15(4) Pages: 225-234
  • Peer Reviewed
• [Journal Article] Optimization of a Prominent Oxygen-Permeable Device for Pancreatic Islets (2008)
  • Author(s): Goto M, Yoshikawa Y, Matsuo K, Shirasu A, Ogawa N, Takahashi H, Saitoh Y, Fujimori K, Kurokawa Y, Tamai M, Satomi S
  • Journal Title: Transplantation Proc Volume: 40(2) Pages: 411-412
  • Peer Reviewed
• [Journal Article] Influence of a current style of culture on the quality of isolated pancreatic islets (2008)
  • Author(s): Takahashi H, Goto M, Ogawa N, Saitoh Y, Fujimori K, Kurokawa Y, Doi H, Satomi S
  • Journal Title: Transplantation Proc Volume: 40(2) Pages: 358-359
  • Peer Reviewed
• [Journal Article] Institutional indications for islet transplantation after total pancreatectomy (2008)
  • Author(s): Sakata N, Egawa S, Motoi F, Mikami Y, Ishida M, Aoki T, Ottomo S, Fukuyama S, Rikiyama T, Katayose Y, Goto M, Unno M
  • Journal Title: J Hepatobiliary Pancreat Surg Volume: 15(5) Pages: 488-492
  • Peer Reviewed
• [Journal Article] Low molecular weight dextran sulfate導入が引き起こす移植後膵島グラフト生着促進による、一型糖尿病根治療法としての膵島移植の確立 (2008)
  • Author(s): 後藤昌史
  • Journal Title: 臨床薬理の進歩 Volume: 29 Pages: 206-214
  • Peer Reviewed
• [Presentation] 膵動静脈奇形に起因する急性腹膜炎に対しグラフト保護プロトコールの導入により良好な結果を得た自家膵島移植症例の報告 (2011)
  • Author(s): 後藤昌史、坂田直昭、山谷英之、元井冬彦、山口賢、猪村武弘、稲垣明子、伊藤経夫、林洋毅、石垣泰、片桐秀樹、長谷川豊、澤田正二郎、廣田衛久、下瀬川徹、関口悟、藤盛啓成、江川新一、海野倫明、里見進
  • Organizer: 第38回膵膵島移植研究会
  • Place of Presentation: 奈良
  • Year and Date: 2011-03-05
• [Presentation] A Study on the Influence and Control of Ischemic Stress during Pancreas Preservation on Isolated Islets (2011)
  • Author(s): Feng Zhaoqiang, Masafumi Goto, Takehiro Imura, Akiko Inagaki, Hideyuki Yamaya, Yoshimochi Kurokawa, Satoshi Sekiguchi, Keisei Fujimori, Junji Yodoi, Susumu Satomi
  • Organizer: 第38回膵膵島移植研究会
  • Place of Presentation: 奈良
  • Year and Date: 2011-03-05
• [Presentation] イソフルランが膵島移植に及ぼす影響 (2011)
  • Author(s): 山谷英之、後藤昌史、Feng Qiang、猪村武弘、末田輝子、小林英司、関口悟、藤盛啓成、里見進
  • Organizer: 第38回膵膵島移植研究会
  • Place of Presentation: 奈良
  • Year and Date: 2011-03-05
• [Presentation] Thioredoxin-1による移植後早期膵島障害の抑制 (2011)
  • Author(s): 阿佐美健吾、後藤昌史、猪村武弘、稲垣明子、関口悟、藤盛啓成、淀井淳司、里見進
  • Organizer: 第38回膵膵島移植研究会
  • Place of Presentation: 奈良
  • Year and Date: 2011-03-05
• [Presentation] インスリン及び中心静脈栄養によるrestingが膵島移植後のグラフト生着へ及ぼす影響 (2011)
  • Author(s): 神保琢也、後藤昌史、猪村武弘、関口悟、藤盛啓成、里見進
  • Organizer: 第38回膵膵島移植研究会
  • Place of Presentation: 奈良
  • Year and Date: 2011-03-05
• [Presentation] 膵島を含有するシート作製方法の検討 (2011)
  • Author(s): 稲垣明子、後藤昌史、大橋一夫、里見進
  • Organizer: 第10回日本再生医療学会
  • Place of Presentation: 東京
  • Year and Date: 2011-03-01
• [Presentation] 膵島移植の現状と今後の展望 (2010)
  • Author(s): 後藤昌史
  • Organizer: 第13回近畿膵移植検討会
  • Place of Presentation: 大阪
  • Year and Date: 2010-12-04
• [Presentation] 膵島分離におけるTLA活性の意義に関する検討 (2010)
  • Author(s): 後藤昌史、山形洋平、渡邉君子、村山和隆、猪村武弘、稲垣明子、山谷英之、黒川良望、里見進
  • Organizer: 第37回日本臓器保存生物医学会
  • Place of Presentation: 新潟
  • Year and Date: 2010-11-20
• [Presentation] 過冷却状態が膵組織保存へ及ぼす影響に関する検討 (2010)
  • Author(s): 猪村武弘、後藤昌史、藤井和博、大和田哲男、黒川良望、里見進
  • Organizer: 第37回日本臓器保存生物医学会
  • Place of Presentation: 新潟
  • Year and Date: 2010-11-20
• [Presentation] イソフルランが膵島移植に及ぼす影響 (2010)
  • Author(s): 山谷英之、後藤昌史、Feng Zhaoqiang、猪村武弘、末田輝子、里見進
  • Organizer: 第37回日本臓器保存生物医学会
  • Place of Presentation: 新潟
  • Year and Date: 2010-11-20
• [Presentation] Impact of ischemic stress on the quality of isolated islets (2010)
  • Author(s): Feng Zhaoqiang, Masafumi Goto, Takehiro Imura, Akiko Inagaki, Hideyuki Yamaya1, Yoshimochi Kurokawa, Junji Yodoi, Susumu Satomi
  • Organizer: 第37回日本臓器保存生物医学会
  • Place of Presentation: 新潟
  • Year and Date: 2010-11-20
• [Presentation] イソフルランが膵島移植におけるグラフト生着へ及ぼす影響に関する検討 (2010)
  • Author(s): 山谷英之、後藤昌史、Feng Qiang、猪村武弘、末田輝子、里見進
  • Organizer: 第46回日本移植学会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-21
• [Presentation] No Need of Tryptic-like Activity for Successful Porcine Islet Isolation (2010)
  • Author(s): Masafumi Goto, Youhei Yamagata, Kimiko Watanabe, Kazutaka Murayama, Takehiro Imura, Akiko Inagaki, Hideyuki Yamaya, Keisei Fujimori, Yoshimochi Kurokawa, Susumu Satomi
  • Organizer: 2010 XXIII International Congress Of The Transplantation Society
  • Place of Presentation: Canada, Vancouver
  • Year and Date: 2010-08-16
• [Presentation] Interruption of a cross-talk between the complement and coagulation cascades improves early outcomes after intraportal islet transplantation (2010)
  • Author(s): Kazuaki Tokodai, Masafumi Goto, Akiko Inagaki, Wataru Nakanishi, Noriko Okada, Hidechika Okada, Susumu Satomi
  • Organizer: 2010 XXIII International Congress Of The Transplantation Society
  • Place of Presentation: Canada, Vancouver
  • Year and Date: 2010-08-16
• [Presentation] 移植後早期膵島障害の抑制を目的とした新規プロトコールの有効性の評価および作用機序の解明 (2010)
  • Author(s): 戸子台和哲、後藤昌史、稲垣明子、中西渉、岡田則子、岡田秀親、里見進
  • Organizer: 第37回膵膵島移植研究会
  • Place of Presentation: 宇都宮
  • Year and Date: 2010-03-13
• [Presentation] 長期冷保存を伴う膵島移植を対象とした臓器保存溶液に関する検討C (2010)
  • Author(s): 猪村武弘、後藤昌史、藤盛啓成、黒川良望、里見進
  • Organizer: 第37回膵膵島移植研究会
  • Place of Presentation: 宇都宮
  • Year and Date: 2010-03-13
• [Presentation] A STRONG CANDIDATE APPROACH TO PREVENT THE INSTANT BLOOD-MEDIATED INFLAMMATORY REACTION IN CLINICAL ISLET TRANSPLANTATION (2009)
  • Author(s): Kazuaki Tokodai, Masafumi Goto, Akiko Inagaki, Wataru Nakanishi, Noriko Okada, Hidechika Okada, Susumu Satomi
  • Organizer: 2009 International Pancreas and Islet Transplant Association
  • Place of Presentation: Italy, Venice
  • Year and Date: 2009-10-13
• [Presentation] Potency tests for assessing the quality of isolated pancreatic islets (2009)
  • Author(s): Masafumi Goto
  • Organizer: The 10th Cell Transplant Society Congress
  • Place of Presentation: Okayama
  • Year and Date: 2009-04-20