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Development of a basis for establishing the ultimate transplantation medicine that does not require the administration of immunosuppressive drugs

Research Project

Project/Area Number 18H04056
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research InstitutionTohoku University

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 稲垣 明子  東北大学, 医学系研究科, 助教 (20360224)
村山 和隆  東北大学, 医工学研究科, 准教授 (40400452)
木村 睦  信州大学, 学術研究院繊維学系, 教授 (60273075)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥44,070,000 (Direct Cost: ¥33,900,000、Indirect Cost: ¥10,170,000)
Fiscal Year 2021: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2020: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2019: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2018: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Keywords膵島移植 / 肝細胞移植 / 細胞デバイス / 免疫抑制剤 / 皮下移植 / 新生血管 / 免疫隔離
Outline of Final Research Achievements

This study was conducted to establish the basis of transplantation medicine that does not require immunosuppressants by combining a new transplantation method to subcutaneous space, which is an ideal transplant site, with an immunoisolated cell device. As a result, it has been clarified that we could cure diabetes for more than 6 months without need of immunosuppressants even in a rat diabetic model, by implanting a gelatin hydrogel nonwoven fabric (GHNF) into the subcutaneous space as pre-treatment, then replacing it with pancreatic islets encapsulated in a novel immunoisolated cell device consisting of modified polyvinyl alcohol. It was also revealed that the dramatic effect of GHNF is due not only to the construction of new blood vessels but also to the compensation of various extracellular matrices and various growth factors derived from host cells (IGF-2, HGF, etc.).

Academic Significance and Societal Importance of the Research Achievements

本研究によって開発した免疫隔離細胞デバイスは、マウスにおいて1年以上、より大型動物であるラットにおいても半年以上と、長期間に渡り免疫抑制剤非使用下で糖尿病治療が可能であることを実証した革新的移植ツールである。ただ長期に作用するのみではなく、この卓越した効果が、最も移植困難とされている皮下において実現できたことに大きな学術的意義がある。この開発デバイスを実用化することにより、免疫抑制剤による副作用の回避、医療費の軽減、安全性の担保といった絶対的メリットを患者へもたらすことが可能となり、現在の再生医療が抱える課題を一気に払拭し、再生医療を推進していく上で大きな社会的意義を有していると考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (50 results)

All 2022 2021 2020 2019 2018

All Journal Article (25 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 25 results,  Open Access: 14 results) Presentation (20 results) (of which Invited: 10 results) Patent(Industrial Property Rights) (5 results) (of which Overseas: 5 results)

  • [Journal Article] Mesenchymal stem cells secretions enhanced ATP generation on isolated islets during transplantation2022

    • Author(s)
      Teratani T, Kasahara N, Fujimoto Y, Sakuma Y, Miki A, Goto M, Sata N, Kitayama J
    • Journal Title

      Islets

      Volume: 14 Issue: 1 Pages: 69-81

    • DOI

      10.1080/19382014.2021.2022423

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Distribution of amniotic epithelial cells after intraportal infusion in a rat model2022

    • Author(s)
      Tanaka M, Tokodai K, Sato M, Yamada S, Okita H, Ito T, Saito M, Hoshiai T, Miyagi S, Miki T, Unno M, Kamei T, Goto M
    • Journal Title

      Transplantation Proceedings

      Volume: - Issue: 2 Pages: 513-515

    • DOI

      10.1016/j.transproceed.2021.09.077

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short-term inhalation of isoflurane improves the outcomes of intraportal hepatocyte transplantation2022

    • Author(s)
      Nishimaki H, Saitoh Y, Inagaki A, Nakamura Y, Imura T, Fathi I, Yamana H, Ohashi K, Miyagi S, Kamei T, Unno M, Goto M
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 4241-4241

    • DOI

      10.1038/s41598-022-08237-6

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] KRP-203 is a Desirable Immunomodulator for Islet Allotransplantation2021

    • Author(s)
      Fathi I, Nishimura R, Imura T, Inagaki A, Kanai N, Ushiyama A, Kikuchi M, Maekawa M, Yamaguchi H, Goto M
    • Journal Title

      Transplantation

      Volume: - Issue: 5 Pages: 963-972

    • DOI

      10.1097/tp.0000000000003870

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optimization of dye solutions for detecting damaged pancreatic tissues during islet isolation procedures2021

    • Author(s)
      Imura T, Inagaki A, Igarashi Y, Goto M
    • Journal Title

      PLOS ONE

      Volume: 16 Issue: 8 Pages: e0255733-e0255733

    • DOI

      10.1371/journal.pone.0255733

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preferable transplant site for hepatocyte transplantation in a rat model2021

    • Author(s)
      Ogasawara H, Inagaki A, Fathi I, Imura T, Yamana H, Saitoh Y, Matsumura M, Fukuoka K, Miyagi S, Nakamura Y, Ohashi K, Unno M, Kamei T, Goto M
    • Journal Title

      Cell Transplantation

      Volume: Jan-Dec 30

    • DOI

      10.1177/09636897211040012

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decellularized whole-organ pre-vascularization: A novel approach for organogenesis2021

    • Author(s)
      Fathi I, Imura T, Inagaki A, Nakamura Y, Nabawi A, Goto M
    • Journal Title

      Frontiers in Bioengineering and Biotechnology

      Volume: 9 Pages: 756755-756755

    • DOI

      10.3389/fbioe.2021.756755

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The liver surface is an attractive transplantation site for pancreatic islet transplantation2021

    • Author(s)
      Inagaki A, Imura T, Nakamura Y, Ohashi K, Goto M
    • Journal Title

      Journal of Clinical Medicine

      Volume: 10(4) Issue: 4 Pages: 724-724

    • DOI

      10.3390/jcm10040724

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improvement of hepatocyte engraftment by co-transplantation with pancreatic islets in hepatocyte transplantation2021

    • Author(s)
      Saitoh Y, Inagaki A, Fathi I, Imura T, Nishimaki H, Ogasawara H, Matsumura M, Miyagi S, Yasunami Y, Unno M, Kamei T, Goto M
    • Journal Title

      J Tissue Eng Regen Med

      Volume: Jan 23 Issue: 4 Pages: 1-14

    • DOI

      10.1002/term.3170

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of re-augmenting maintenance immunosuppression on post-transplant donor-specific HLA antibodies in liver transplantation2020

    • Author(s)
      Tokodai K, Miyagi S, Nakanishi W, Fujio A, Kashiwadate T, Goto M, Unno M, Kamei T
    • Journal Title

      Transpl Immunology

      Volume: Sep 9 Pages: 101334-101334

    • DOI

      10.1016/j.trim.2020.101334

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Short-Term Normothermic and Subnormothermic Perfusion After Cold Preservation on Liver Transplantation From Donors After Cardiac Death2020

    • Author(s)
      Yamada S, Miyagi S, Hara Y, Kakizaki Y, Sasajima H, Mitsui K, Fujimori K, Unno M, Kamei T, Goto M
    • Journal Title

      Transplantation Proc

      Volume: 52(6) Issue: 6 Pages: 1639-1642

    • DOI

      10.1016/j.transproceed.2020.01.147

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cytoprotective Effects of Mesenchymal Stem Cells During Liver Transplantation From Donors After Cardiac Death in Swine2020

    • Author(s)
      Sasajima H, Miyagi S, Yamada S, Kakizaki Y, Kamei T, Unno M, Goto M
    • Journal Title

      Transplantation Proc

      Volume: 52(6) Issue: 6 Pages: 1891-1900

    • DOI

      10.1016/j.transproceed.2020.01.165

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Collagenases in pancreatic islet isolation2020

    • Author(s)
      Fathi I, Goto M
    • Journal Title

      Transplantation, Bioengineering, and Regeneration of the Endocrine Pancreas

      Volume: 1 Issue: 3 Pages: 529-546

    • DOI

      10.21926/obm.transplant.1903071

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Successful ABO-Incompatible Adult Liver Transplantation in a Recipient With High Preoperative Immunoglobulin G Antibody Titer: A Case Report2020

    • Author(s)
      Saitoh Y, Miyagi S, Nakanishi C, Tokodai K, Nakanishi W, Nichimura R, Fujio A, Shimizu K, Fukuoka K, Kumata H, Matsumura M, Goto M, Kamei T, Unno M
    • Journal Title

      Transplantation Proc

      Volume: 印刷中

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Characteristics and predictive value for graft fibrosis of the complement-binding capacity of donor-specific human leukocyte antigen antibodies after pediatric liver transplantation2019

    • Author(s)
      Tokodai K, Miyagi S, Nakanishi W, Nishimura R, Fujio A, Goto M, Unno M, Kamei T
    • Journal Title

      Pediatr Transplant

      Volume: Dec 29 Issue: 1

    • DOI

      10.1111/petr.13648

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 糖尿病と再生医療2019

    • Author(s)
      後藤昌史
    • Journal Title

      Diabetes Strategy

      Volume: 9 Pages: 5-20

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A simple and useful predictive assay for evaluating the quality of isolated hepatocytes for hepatocyte transplantation2019

    • Author(s)
      Matsumura M, Imura T, Inagaki A, Ogasawara H, Fukuoka K, Fathi I, Miyagi S, Ohashi K, Unno M, Kamei T, Satomi S, Goto M
    • Journal Title

      Scientific Reports

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Strategy towards tailored donor tissue-specific pancreatic islet isolation2019

    • Author(s)
      Miyazaki Y, Murayama K, Fathi I, Imura T, Yamagata Y, Watanabe K, Maeda H, Inagaki A, Igarashi Y, Miyagi S, Shima H, Igarashi K, Kamei T, Unno M, Goto M
    • Journal Title

      PLOS ONE

      Volume: 印刷中

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pediatric Living-Donor Liver Transplant Recipients without Transition After Reaching Adulthood2019

    • Author(s)
      Nakanishi C1, Miyagi S1, Tokodai K1, Nakanishi W1, Nishimura R1, Goto M2, Unno M1, Kamei T1.
    • Journal Title

      Ann Transplant. 2019 Jan 8;24:18-24

      Volume: 24 Pages: 18-24

    • DOI

      10.12659/aot.911544

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Current status of islet autotransplantation2018

    • Author(s)
      Goto M
    • Journal Title

      Nippon Shokakibyo Gakkai Zasshi

      Volume: 115 Issue: 8 Pages: 706-712

    • DOI

      10.11405/nisshoshi.115.706

    • NAID

      130007432149

    • ISSN
      0446-6586, 1349-7693
    • Year and Date
      2018-08-10
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of Middle Hepatic Vein Tributaries Preserving Technique Until Just Before Graft Retrieval on Donors' Surgical Outcomes in Living Donor Liver Transplantation.2018

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

      Transplant Proc. 2018 Jun;50(5):1538-1543.

      Volume: 50(5) Issue: 5 Pages: 1538-1543

    • DOI

      10.1016/j.transproceed.2018.02.061

    • Related Report
      2018 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
      2018 Annual Research Report
    • Peer Reviewed
  • [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
      2018 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
      2018 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
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 膵島移植2021

    • Author(s)
      後藤昌史
    • Organizer
      日本消化器病学会第2回再生医療セミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 幹細胞移植や異種移植などの膵島移植代用治療を促進する細胞デバイスの開発2021

    • Author(s)
      後藤昌史
    • Organizer
      第49回日本膵・膵島移植学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 膵島移植と再生医療のクロストーク2021

    • Author(s)
      後藤昌史
    • Organizer
      第21回日本再生医療学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 不織布構造ゼラチン基材の導入による経門脈移植を凌駕する革新的皮下膵島移植法の確立2021

    • Author(s)
      金井 哲史,稲垣 明子,中村 保宏,猪村 武弘,Ibrahim Fathi,三頭 啓明,斎藤 竜助,宮城 重人,亀井 尚,海野 倫明,田畑 泰彦,後藤 昌史
    • Organizer
      第48回日本膵膵島移植研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 皮下膵島移植における低酸素環境改善に役立つ新規組織内酸素濃度測定方法の確立2021

    • Author(s)
      三頭啓明、猪村武弘、稲垣明子、Fathi Ibrahim、宮城重人、亀井 尚、海野倫明、後藤昌史
    • Organizer
      第48回日本膵膵島移植研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A Preliminary Study of Decellularized Whole-Organ Pre-vascularization: A Novel Approach for Organogenesis2021

    • Author(s)
      Fathi Ibrahim、猪村武弘、稲垣明子、後藤昌史
    • Organizer
      The second Congress of Asian Pancreas and Islet Transplant Association (APITA 2021)
    • Related Report
      2020 Annual Research Report
  • [Presentation] 安全な再生医療実現へ向けた革新的細胞デバイスの構築2021

    • Author(s)
      後藤昌史、稲垣明子 、渡邉君子
    • Organizer
      第20回日本再生医療学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 移植医療と再生医療の融合がもたらす糖尿病医療の今後の展開2020

    • Author(s)
      後藤昌史
    • Organizer
      第56回日本移植学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 新規免疫隔離膵島デバイスの膵島生着効率に関する検証2020

    • Author(s)
      稲垣明子
    • Organizer
      第22回日本異種移植研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 膵島移植の現状と展望2019

    • Author(s)
      後藤昌史
    • Organizer
      日本消化器病学会第1回再生医療セミナー(依頼講演)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Development of a novel immunosuppression-free cell device for pancreatic islet transplantation2019

    • Author(s)
      Masafumi Goto
    • Organizer
      17th International Pancreas and Islet Transplant Association (IPITA 2019)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 糖尿病への細胞移植療法におけるECMの意義2019

    • Author(s)
      後藤昌史
    • Organizer
      第6回 MatriCell フォーラム(依頼講演)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 移植医療と再生医療の融合が切り拓く重症糖尿病治療の近未来2019

    • Author(s)
      後藤昌史
    • Organizer
      岩手1型糖尿病研究会(依頼講演)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 細胞移植と再生医療の融合がもたらす糖尿病への未来型医療2019

    • Author(s)
      後藤昌史
    • Organizer
      第59回日本臨床化学会(依頼講演)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 膵島移植と再生医療の融合を促進する細胞デバイスの開発2019

    • Author(s)
      後藤昌史
    • Organizer
      第55回日本移植学会(ワークショップ)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 糖尿病に対する細胞移植療法の 現状と展望2019

    • Author(s)
      後藤昌史
    • Organizer
      第4回くりこま外科研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 免疫隔離細胞デバイスの開発2019

    • Author(s)
      後藤昌史
    • Organizer
      第21回日本異種移植研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 免疫抑制剤不要の次世代膵島移植実現へ向けた試み2019

    • Author(s)
      後藤昌史
    • Organizer
      第46回日本膵膵島移植研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞凝集塊である膵島を用いた糖尿病移植医療の現状と展望2018

    • Author(s)
      後藤昌史
    • Organizer
      第7回細胞凝集研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 東北大学が目指す膵島移植の次の展開2018

    • Author(s)
      後藤昌史
    • Organizer
      第54回日本移植学会
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] ゼラチン含有デバイス2021

    • Inventor(s)
      後藤昌史、金里脩平、木村佳弘、小原田明信
    • Industrial Property Rights Holder
      後藤昌史、金里脩平、木村佳弘、小原田明信
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-019174
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 移植デバイス2021

    • Inventor(s)
      後藤昌史、金里脩平、木村佳弘、石場啓太、小原田明信
    • Industrial Property Rights Holder
      後藤昌史、金里脩平、木村佳弘、石場啓太、小原田明信
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-019175
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 血管新生デバイス2020

    • Inventor(s)
      後藤昌史、金里脩平、木村佳弘、小原田明信
    • Industrial Property Rights Holder
      後藤昌史、金里脩平、木村佳弘、小原田明信
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-019234
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 血管新生デバイス(方法)2020

    • Inventor(s)
      後藤昌史、金里脩平、木村佳弘、小原田明信
    • Industrial Property Rights Holder
      後藤昌史、金里脩平、木村佳弘、小原田明信
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-019235
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 血管新生デバイス2020

    • Inventor(s)
      後藤昌史
    • Industrial Property Rights Holder
      後藤昌史
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-019234
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
    • Overseas

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Published: 2018-04-23   Modified: 2023-01-30  

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