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Establishment of next-generation diabetes treatment by construction of tailor-made cell isolation system

Research Project

Project/Area Number 15H04916
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionTohoku University

Principal Investigator

Goto Masafumi  東北大学, 医学系研究科, 教授 (50400453)

Co-Investigator(Kenkyū-buntansha) 岡田 秀親  名古屋市立大学, 大学院医学研究科, 名誉教授 (30160683)
山形 洋平  東京農工大学, (連合)農学研究科(研究院), 教授 (40230338)
村山 和隆  東北大学, 医工学研究科, 准教授 (40400452)
Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥10,000,000、Indirect Cost: ¥3,000,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2016: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Keywords膵島移植 / 細胞分離酵素 / 糖尿病 / 移植医療 / 再生医療 / 移植・再生医療 / 酵素
Outline of Final Research Achievements

This study was conducted to establish the basis of "tailor-made islet isolation method" that can correspond to the extracellular matrix component of donor pancreatic tissues. As a result, it has been clarified that the specific target substrates of collagenase G which have not been identified until now are collagens IV and V, and by combining it with the knowledge about the target substrates of collagenase H which has already been identified by our team, it has been reported that it is possible to establish a tailor-made islet isolation method for specific donor species by using animal models. Regarding the neutral proteases, we have revealed that laminin and fibronectin are the main target matrices, and we succeeded in identifying the cleavage epitopes of each of the two newly constructed neutral proteases (ChNP and Clostripain).

Academic Significance and Societal Importance of the Research Achievements

本研究の遂行により、膵島分離用酵素剤を構成する各酵素成分の対象基質を初めて明らかにする事ができた。それにより、これまでの常識である盲目的な酵素量の増加といった姑息的な手法ではなく、脳死ドナーより提供頂く膵組織の基質組成に対応する酵素成分を科学的に至適化するという、時代を先取りするテーラーメイド型膵島分離システムの基盤を構築する事ができた。この研究成果は、質の高い膵島の安定的確保を通じて膵島移植の発展、普及に貢献するものと期待される。また、本研究で基盤を構築したテーラーメイド型細胞分離システムは、膵島移植のみならず様々な再生医療への応用が可能であり、医学的に大きな意義を有していると考えられる。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (43 results)

All 2018 2017 2016 2015

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 5 results,  Acknowledgement Compliant: 1 results) Presentation (29 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Book (2 results)

  • [Journal Article] A novel subcutaneous site of islet transplantation superior to the liver2018

    • Author(s)
      Yasunami Y, Nakafusa Y, Nitta N, Nakamura M, Goto M, Ono J, Taniguchi M
    • Journal Title

      Transplantation

      Volume: - Issue: 6 Pages: 945-952

    • DOI

      10.1097/tp.0000000000002162

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of post-transplant donor-specific HLA antibody with liver graft fibrosis during long-term follow-up after pediatric liver transplantation.2018

    • Author(s)
      Tokodai K, Miyagi S, Nakanishi C, Hara Y, Nakanishi W, Miyazawa K, Shimizu K, Murakami K, Sasano H, Goto M, Unno M, Kamei T.
    • Journal Title

      Pediatric Transplantation

      Volume: - Issue: 3

    • DOI

      10.1111/petr.13169

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effects of short-term subnormothermic perfusion after cold preservation on liver grafts from donors after cardiac death: An ex vivo rat model2018

    • Author(s)
      Kakizaki Y, Miyagi S, Shimizu K, Miyazawa K, Nakanishi W, Tokodai K, Hara Y, Nakanishi C, Unno M, Kamei T, Goto M, Satomi S
    • Journal Title

      Transplantation

      Volume: 102 Issue: 4 Pages: e147-e154

    • DOI

      10.1097/tp.0000000000002080

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Optimization of the Prevascularization Procedures for Improving Subcutaneous Islet Engraftment.2018

    • Author(s)
      Uematsu SS, Inagaki A, Nakamura Y, Imura T, Igarashi Y, Fathi I, Miyagi S, Ohuchi N, Satomi S, Goto M.
    • Journal Title

      Transplantation. 2018 Mar;102(3):387-395

      Volume: 102(3) Issue: 3 Pages: 387-395

    • DOI

      10.1097/tp.0000000000001970

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Renoportal Anastomosis in Left Lateral Lobe Living Donor Liver Transplantation: A Pediatric Case2017

    • Author(s)
      Ogasawara H、Nakanishi C、Miyagi S、Tokodai K、Hara Y、Nakanishi W、Miyazawa K、Shimizu K、Kumata H、Goto H、Goto M、Unno M、Kamei T
    • Journal Title

      Case Rep Gastroenterol

      Volume: 11 Issue: 3 Pages: 584-592

    • DOI

      10.1159/000481160

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Controlled basic fibroblast growth factor release device made of poly(ethyleneglycol) dimethacrylates for creating a subcutaneous neovascular bed for cell transplantation2017

    • Author(s)
      Yamada Shinji、Nagai Nobuhiro、Saijo Saaya、Kaji Hirokazu、Nishizawa Matsuhiko、Imura Kozue、Goto Masafumi、Abe Toshiaki
    • Journal Title

      Journal of Biomedical Materials Research Part B: Applied Biomaterials

      Volume: 105 Issue: 11 Pages: 3017-3024

    • DOI

      10.1002/jbm.a.36153

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The utility of superb microvascular imaging for monitoring low-velocity venous flow following pancreas transplantation: report of a case2017

    • Author(s)
      Tokodai K、Miyagi S、Nakanishi C、Hara Y、Nakanishi W、Miyazawa K、Shimizu K、Goto M、Kamei T、Unno M
    • Journal Title

      J Med Ultrason

      Volume: 45 Issue: 1 Pages: 171-174

    • DOI

      10.1007/s10396-017-0795-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The optimization of short-term hepatocyte preservation prior to transplantation2017

    • Author(s)
      Fukuoka K, Inagaki A, Nakamura Y, Matsumura M, Yoshida S, Imura T, Igarashi Y, Miyagi S, Ohashi K, Enosawa S, Kamei T, Unno M, Ohuchi N,Satomi S, Goto M
    • Journal Title

      Transplantation Direct

      Volume: in press

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Supplemental Analysis for N-linked Sugars in Adult Pig Islets2016

    • Author(s)
      Eguchi H, Kawamura T, Kashiyama N, Matsuura R, Sakai R, Nakahata K, Lo PC, Asada M, Maeda A, Goto M, Toyoda M, Okuyama H, Miyagawa S
    • Journal Title

      Transplantation Proc

      Volume: 48 Pages: 1302-1303

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 3.Collagen V is a potential substrate for clostridial collagenase G in pancreatic islet isolation2016

    • Author(s)
      ShimaH, Inagaki A, Imura T, Yamagata Y, Watanabe K, Igarashi K, Goto M, Murayama K
    • Journal Title

      Journal of Diabetes Research

      Volume: 2016 Pages: 4396756-4396756

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 1.Collagen V is a potential substrate for clostridial collagenase G in pancreatic islet isolation2016

    • Author(s)
      ShimaH, Inagaki A, Imura T, Yamagata Y, Watanabe K, Igarashi K, Goto M, Murayama K
    • Journal Title

      Journal of Diabetes Research

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 2.Cloning a neutral protease of Clostridium histolyticum, determining its substrate specificity, and designing a specific substrate2015

    • Author(s)
      Maeda H, Nakagawa K, Murayama K, Goto M, Watanabe K, Takeuchi M, Yamagata Y
    • Journal Title

      Applied Microbiology and Biotechnology

      Volume: 99 Issue: 24 Pages: 10489-10499

    • DOI

      10.1007/s00253-015-6923-4

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] 工業グレードへスケールアップした新規中性プロテアーゼの膵島分離における安全性及び有効性に関する検証2018

    • Author(s)
      猪村武弘
    • Organizer
      第45回日本膵膵島移植研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ドナー膵組織のマトリックス組成に対応するテーラーメイド型膵島分離法の確立へ向けた試み2018

    • Author(s)
      宮﨑勇希
    • Organizer
      第45回日本膵膵島移植研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵島分離に用いる新規中性プロテアーゼ 2 種の品質評価に有用な特異的基質の同定2018

    • Author(s)
      前田 浩
    • Organizer
      第45回日本膵膵島移植研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 高純度組換え体ラット膵臓カルボキシペプチダーゼ製剤の作出2018

    • Author(s)
      前田 浩
    • Organizer
      日本農芸化学会2018年度
    • Related Report
      2017 Annual Research Report
  • [Presentation] 東北大学における次世代膵島移植確立へ向けた技術革新2017

    • Author(s)
      後藤 昌史、稲垣 明子、山形 洋平、村山 和隆、渡邉 君子、前田 浩、猪村 武弘、五十嵐 康宏、植松 智海、宮崎 勇希、水井 崇浩、戸子台 和哲、宮城 重人、角 昭一郎、藤盛 啓成、大内 憲明、里見 進
    • Organizer
      第44回日本膵膵島移植研究会
    • Place of Presentation
      京都 (京都大学芝蘭会館)
    • Year and Date
      2017-03-10
    • Related Report
      2016 Annual Research Report
  • [Presentation] 安全で高性能な細胞分離酵素剤の開発による膵島移植の技術革新2017

    • Author(s)
      後藤昌史
    • Organizer
      第16回日本再生医療学会
    • Place of Presentation
      仙台 (仙台国際センター)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 次世代膵島移植確立へ向けた試み2017

    • Author(s)
      後藤昌史
    • Organizer
      第16回日本組織移植学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 免疫抑制剤不要の膵島移植実現へ向けて2017

    • Author(s)
      後藤昌史
    • Organizer
      第53回日本移植学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 国産GMP準拠のコラゲナーゼによるヒト肝細胞分離2017

    • Author(s)
      絵野沢 伸
    • Organizer
      第53回日本移植学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 膵島移植の最新状況と今後の展望2017

    • Author(s)
      後藤昌史
    • Organizer
      第5回Tokyo Islet Research Conference
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 膵島移植の現状と今後の展望2017

    • Author(s)
      後藤昌史
    • Organizer
      第15回1型糖尿病研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 膵消化酵素が膵島分離工程で膵島に与える影響2016

    • Author(s)
      宮崎勇希、猪村武弘、山形洋平,前田 浩、村山和隆,渡邉君子,稲垣明子,五十嵐康宏、大内憲明、里見 進、後藤昌史
    • Organizer
      第43回日本臓器保存生物医学会
    • Place of Presentation
      東京 (品川プリンスホテル)
    • Year and Date
      2016-11-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] 実用化へ向けた膵島分離用新規中性プロテアーゼカクテルの構築2016

    • Author(s)
      後藤昌史
    • Organizer
      第52回日本移植学会
    • Place of Presentation
      東京 (品川プリンスホテル)
    • Year and Date
      2016-09-29
    • Related Report
      2016 Annual Research Report
  • [Presentation] The influence of dissociation enzymes on isolated islets during pancreatic islet isolation procedures2016

    • Author(s)
      Yuki Miyazaki, Takehiro Imura, Youhei Yamagata, Hiroshi Maeda, Kazutaka Murayama, Kimiko Watanabe, Akiko Inagaki, Yasuhiro Igarashi, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
    • Organizer
      26th International Congress of The Transplantation Society (2016)
    • Place of Presentation
      Hong Kong (CHINA)
    • Year and Date
      2016-08-18
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The investigation on target matrix of collagenase G for achieving tailor-made islet isolation2016

    • Author(s)
      Satoru Yoshida, Youhei Yamagata, Kanako Nakagawa, Kazuhisa Maeda, Kazutaka Murayama, Kimiko Watanabe, Takehiro Imura, Akiko Inagaki, Yasuhiro Igarashi, Shigehito Miyagi, Kazuo Ohashi, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
    • Organizer
      26th International Congress of The Transplantation Society (2016)
    • Place of Presentation
      Hong Kong (CHINA)
    • Year and Date
      2016-08-18
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 新規リコンビナント型コラゲナーゼの膵島移植への臨床応用2016

    • Author(s)
      後藤昌史,山形洋平,村山和隆,渡邉君子,前田 浩,猪村武弘,稲垣明子,五十嵐康宏、宮城重人、Olle Korsgren、大内憲明、里見 進
    • Organizer
      第116回日本外科学会
    • Place of Presentation
      大阪 (リーガロイヤルホテル大阪)
    • Year and Date
      2016-04-14
    • Related Report
      2016 Annual Research Report
  • [Presentation] 膵島分離成否の鍵を握る中性プロテアーゼ使用法に関する戦略2016

    • Author(s)
      後藤昌史,山形洋平,村山和隆,渡邉君子,前田 浩,猪村武弘,稲垣明子,五十嵐康宏、佐藤真実、宮崎勇希、植松智海、宮城重人、藤盛啓成、大内憲明、里見 進
    • Organizer
      第43回日本膵膵島移植研究会
    • Place of Presentation
      ホテルグランビア広島(広島県広島市)
    • Year and Date
      2016-03-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膵島分離工程において消化酵素剤が分離膵島へ及ぼす影響2016

    • Author(s)
      宮崎勇希、猪村武弘、山形洋平,前田 浩、村山和隆,渡邉君子,稲垣明子,五十嵐康宏、大内憲明、里見 進、後藤昌史
    • Organizer
      第43回日本膵膵島移植研究会
    • Place of Presentation
      ホテルグランビア広島(広島県広島市)
    • Year and Date
      2016-03-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] テーラーメイド膵島分離実現へ向けたコラゲナーゼサブタイプGの対象基質の検証2016

    • Author(s)
      吉田 諭、山形洋平、中川香奈子、前田憲寿、村山和隆、渡邉君子、猪村武弘、稲垣明子、五十嵐康宏、宮城重人、大橋一夫、大内憲明、里見 進、後藤昌史
    • Organizer
      第43回日本膵膵島移植研究会
    • Place of Presentation
      ホテルグランビア広島(広島県広島市)
    • Year and Date
      2016-03-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 高濃度コラゲナーゼが膵島分離へ及ぼす影響に関する検討2016

    • Author(s)
      猪村武弘、山形洋平、村山和隆、渡邉君子、稲垣明子、五十嵐康宏、里見 進、後藤昌史
    • Organizer
      第43回日本膵膵島移植研究会
    • Place of Presentation
      ホテルグランビア広島(広島県広島市)
    • Year and Date
      2016-03-04
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膵島移植の現状と今後の展望2016

    • Author(s)
      後藤昌史
    • Organizer
      Diabetes Front Meeting in Morioka
    • Place of Presentation
      盛岡 (盛岡グランドホテル)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Proof of concept for the clinical application of animal component free recombinant collagenase for isolating pancreatic islets2015

    • Author(s)
      Masafumi Goto, Andrew Friberg, Magnus Stahle, Takehiro Imura, Youhei Yamagata, Kimiko Watanabe,Kazutaka Murayama, Akiko Inagaki, Yasuhiro Igarashi, Susumu Satomi, Olle Korsgren
    • Organizer
      2015 International Pancreas and Islet Transplant Association (IPITA)
    • Place of Presentation
      Melbourne (オーストラリア)
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The influence of the synergistic effect of neutral protease derived from Clostridium histolyticum and clostripain on the hepatocyte isolation2015

    • Author(s)
      Satoru Yoshida, Youhei Yamagata, Kazutaka Murayama, Kimiko Watanabe,Takehiro Imura, Yasuhiro Igarashi, Akiko Inagaki, Shigehito Miyagi, Kazuo Ohashi,Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
    • Organizer
      2015 International Pancreas and Islet Transplant Association (IPITA)
    • Place of Presentation
      Melbourne(オーストラリア)
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization and optimization of enzyme components for hepatocyte isolation2015

    • Author(s)
      Satoru Yoshida, Youhei Yamagata, Kanako Nakagawa, Kazutaka Murayama, Kimiko Watanabe, Takehiro Imura, Yasuhiro Igarashi, Akiko Inagaki, Shigehito Miyagi, Kazuo Ohashi, Noriaki Ohuchi, Susumu Satomi, Masafumi Goto
    • Organizer
      2015 International Pancreas and Islet Transplant Association (IPITA)
    • Place of Presentation
      Melbourne(オーストラリア)
    • Year and Date
      2015-11-15
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 安全で高性能な新規膵島分離用酵素剤のヒト膵臓におけるPOC樹立および今後の戦略2015

    • Author(s)
      後藤昌史,山形洋平,村山和隆,渡邉君子,前田 浩,猪村武弘,稲垣明子,五十嵐康宏、宮城重人、田頭真実、藤盛啓成、Olle Korsgren、大内憲明、里見 進
    • Organizer
      第51回日本移植学会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肝細胞分離における細胞分離酵素成分の役割解明と至適化2015

    • Author(s)
      吉田 諭、山形洋平、中川香奈子、村山和隆、渡邉君子、猪村武弘、稲垣明子、五十嵐康宏、宮城重人、大橋一夫、大内憲明、里見 進、後藤昌史
    • Organizer
      第51回日本移植学会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肝細胞分離における中性プロテアーゼとクロストリパインの併用の有効性に関する検証2015

    • Author(s)
      吉田 諭、山形洋平、村山和隆、渡邉君子、猪村武弘、稲垣明子、五十嵐康宏、宮城重人、大橋一夫、大内憲明、里見 進、後藤昌史
    • Organizer
      第51回日本移植学会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 膵島分離酵素剤が膵島へ及ぼす影響2015

    • Author(s)
      猪村武弘,山形洋平,村山和隆,渡邉君子,前田 浩,稲垣明子,五十嵐康宏、後藤昌史
    • Organizer
      第51回日本移植学会
    • Place of Presentation
      ホテル日航熊本(熊本県熊本市)
    • Year and Date
      2015-10-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肝細胞分離用酵素剤の至適化2015

    • Author(s)
      吉田 諭、山形洋平、中川香奈子、村山和隆、渡邉君子、猪村武弘、稲垣明子、五十嵐康宏、宮城重人、大橋一夫、大内憲明、里見 進、後藤昌史
    • Organizer
      第14回日本組織移植学会
    • Place of Presentation
      シティプラザ大阪(大阪府大阪市)
    • Year and Date
      2015-08-29
    • Related Report
      2015 Annual Research Report
  • [Book] 胆道・膵疾患診療の最前線(著書)2017

    • Author(s)
      後藤昌史
    • Publisher
      中山書店
    • Related Report
      2016 Annual Research Report
  • [Book] 新膵臓病学2015

    • Author(s)
      後藤昌史
    • Total Pages
      4
    • Publisher
      南江堂
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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