Establishment of pancreatic islet xenotransplantation as a cure for type 1 diabtes

• Project/Area Number: 18390339
• 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: FUJIMORI Keisei Tohoku University, 病院, 准教授 (50238622)
• Co-Investigator(Kenkyū-buntansha): GOTO Masafumi 東北大学, 国際高等研究教育機構, 准教授 (50400453) ; SEKIGUCHI Satoshi 東北大学, 病院, 助教 (20312580) ; KAWAGISHI Naoki 東北大学, 病院, 講師 (00333807) ; DOI Hideyuki 東北大学, 病院, 准教授 (90188839)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥3,360,000); Fiscal Year 2008: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000); Fiscal Year 2007: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2006: ¥3,900,000 (Direct Cost: ¥3,900,000)
• Keywords: 膵島移植 / 重症糖尿病 / 異種移植 / グラフト障害 / 糖尿病 / 免疫寛容 / 抗体 / IBMIR

Research Abstract

本研究において、Low Molecular weight Dextran Sulfate(LMW-DS)が異種膵島移植における移植後非特異的炎症反応を効果的に制御し得ることをサルを用いた前臨床モデルにて実証することに成功した。さらに同種膵島移植における非特異的炎症反応と対比させることにより、異種膵島移植における補体関与の重要性を明らかとし、補体阻害ペプチド剤を加えることにより異種膵島移植における移植後非特異的炎症反応をより効果的に制御し得ることを見出した。また、本研究において基礎的検討の結果、異種膵島移植の至適免疫抑制プロトコールとして臨床応用が望めるプログラフ、デオキシスパーガリン、C5a阻害ペプチド、およびメシル酸ガベキセートの組み合わせが有望であることが判明したため、今後前臨床試験による検討が望まれる。

Research Products

• [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 Pages: 67-68
  • 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 Pages: 311-313
  • 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 64 Pages: 45-45
• [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, Oeawa N. Fuiimori K. Kurokawa Y, Okada H, Satomi S
  • Journal Title: Transplantation Proc 41(1) Pages: 67-68
  • 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 41(1) Pages: 311-313
  • Peer Reviewed
• [Journal Article] 膵島移植の現状と展望 (2009)
  • Author(s): 後藤目史
  • Journal Title: 最新医学 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 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 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 Pages: 358-359
  • Peer Reviewed
• [Journal Article] Dissecting the instant blood-mediated inflammatory reaction in islet xenotransplantation (2008)
  • Author(s): Goto M. Tiernbere 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 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. 42(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, DoiH, Satomi S
  • Journal Title: Transplantation Proc. 42(2) Pages: 358-359
  • Peer Reviewed
• [Journal Article] Low molecular weight dextran sulfate and Compstatin attenuates the instant blood-mediated inflammatory reaction in pig-to-monkey preclinical islet xenotransplantation (2008)
  • Author(s): Goto M, Tjernberg J, Satomi S, Nilsson B, et. al.(total 13)
  • Journal Title: Xenotransplantation (in press)
  • Peer Reviewed
• [Journal Article] Establishment of a novel predictive assay for the viability of isolated pancreatic islets (2006)
  • Author(s): Goto M, Holgersson J, Kumagai-Braesch M, Korsgren O
  • Journal Title: American Journal of Transplantation Pages: 2483-2483
  • Peer Reviewed
• [Journal Article] Low molecular weight dextran sulfate abrogates the allogeneic instant blood mediated inflammatory reaction (IBMIR) : A strong candidate drug to improve clinical islet transplantation (2006)
  • Author(s): Johansson H, Goto M, Siegbahn A, Elgue G, Korsgren O, Nilsson B
  • Journal Title: American Journal of Transplantation Pages: 305-305
  • Peer Reviewed
• [Journal Article] Establishment of a novel predictive assay for the viability of isolated pancreatic islets (2006)
  • Author(s): Goto M, Holgersson J, Kumagai-Braesch M, Korsgren O
  • Journal Title: American Journal of Transplantation 6 Pages: 2483-2487
• [Journal Article] Low molecular weight dextran sulfate abrogates the allogeneic instant blood mediated inflammatory reaction (IBMIR) : A strong candidate drug to improve clinical islet transplantation (2006)
  • Author(s): Johansson H, Goto M, Siegbahn A, Elgue G, Korsgren O, Nilsson B
  • Journal Title: American Journal of Transplantation 6 Pages: 305-305
• [Journal Article] Establishment of a novel predictive assay for the viability of isolated pancreatic islets (2006)
  • Author(s): Goto M, Holgersson J, Kumagai-Braesch M, Kurokawa Y, Satomi S, Korsgren O
  • Journal Title: Transplantation 82 Pages: 996-996
• [Journal Article] 膵島移植の現況 (2006)
  • Author(s): 後藤昌史, 小川則彦, 関口悟, 藤盛啓成, 黒川良望, 里見 進
  • Journal Title: 宮城腎臓協会会報(話題・トピックス) 3 Pages: 22-31
• [Journal Article] 移植後早期膵島障害に対するp38 mitogen-activated protein kinase inhibitor (FR167653)の有用性 (2006)
  • Author(s): 相磯崇, 赤松順寛, 小川則彦, 後藤昌史, 藤盛啓成, 里見 進
  • Journal Title: 移植 41 Pages: 255-265
  • NAID: 10029277518
• [Presentation] Key issues in islet xenotransplantation (2008)
  • Author(s): Masafumi Goto, Susumu Satomi
  • Organizer: 4th Xenotransplantation Seoul Forum
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2008-11-08
• [Presentation] Key issues in islet xenotransplantation (2008)
  • Author(s): Masafumi Goto, Susumu Satomi
  • Organizer: 4th Xenotransplantation Seoul Forum
  • Place of Presentation: Seoul, korea
  • Year and Date: 2008-11-08
• [Presentation] 東北大学における膵島移植の取り組み (2008)
  • Author(s): 後藤昌史、檜尾好徳、小川則彦、山谷英之、高橋英幸、齋藤之彦、戸子台和哲、関口悟、石原寿光、藤盛啓成、黒川良望、岡芳知、里見進
  • Organizer: 第44回日本移植学会
  • Place of Presentation: 大阪
  • Year and Date: 2008-09-20
• [Presentation] Optimization of a prominent oxygen-permeable device for pancreatic islets (2008)
  • Author(s): Goto M
  • Organizer: 2007 International Pancreas and Islet Transplant Association (IPITA)
  • Place of Presentation: Minneapolis(USA)
  • Year and Date: 2008-09-15
• [Presentation] C5A INHIBITORY PEPTIDE COMBINED WITH GABEXATE MESILATE IS A CLINICALLY AVAILABLE CANDIDATE FOR PREVENTING THE INSTANT BLOOD-MEDIATED INFLAMMATORY REACTION (2008)
  • Author(s): Kazuaki Tokodai, Masafumi Goto, Takehiro Imura, Norihiko Ogawa,Keisei Fujimori, Yoshimochi Kurokawa, Hidechika Okada, Susumu Satomi
  • Organizer: XXII International Congress Of The Transplantation Society
  • Place of Presentation: Sydney,Australia
  • Year and Date: 2008-08-12
• [Presentation] Current status of islet xenotransplantation (2008)
  • Author(s): Goto M
  • Organizer: Keio University Inte rnational Symposium on Cellular Bioengineering 2008
  • Place of Presentation: Tokyo
  • Year and Date: 2008-03-12
• [Presentation] C5A INHIBITORY PEPTIDE COMBINED WITH GABEXATE MESILATE IS A CLINICALLY AVAILABLE CANDIDATE FOR PREVENTING THE INSTANT BLOOD-MEDIATED INFLAMMATORY REACTION (2008)
  • Author(s): Kazuaki Tokodai, Masafumi Goto, Takehiro Imura, Norihiko Ogawa, Keisei Fuiimori, Yoshimochi Kurokawa, Hidechika Okada, and Susumu Satomi
  • Organizer: XXII International Congress Of The Transnlantation Society
  • Place of Presentation: Sydney, Australia
• [Presentation] 膵島移植の現状と展望 (2007)
  • Author(s): 後藤昌史
  • Organizer: 第50回日本糖尿病学会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-24
• [Presentation] 膵島移植-糖尿病根治におけるメディカルイノベーション- (2007)
  • Author(s): 後藤昌史
  • Organizer: 第46回日本生体医工学会
  • Place of Presentation: 仙台
  • Year and Date: 2007-04-25
• [Presentation] 膵島移植 -糖尿病根治におけるメディカルイノベーション- (2007)
  • Author(s): 後藤昌史
  • Organizer: 第46回日本生体医工学会
  • Place of Presentation: 仙台
  • Year and Date: 2007-04-25
• [Patent(Industrial Property Rights)] 移植用膵島の評価方法 (2007)
  • Inventor(s): 後藤昌史、阿部宏之
  • Industrial Property Rights Holder: 独立行政法人東北大学
  • Filing Date: 2007-06-27