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Hybrid transplantation of marginal donor grafts and hepatocytes using biological affinity cell sheet

Research Project

Project/Area Number 16K10417
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionTohoku University

Principal Investigator

Miyazawa Koji  東北大学, 医学系研究科, 非常勤講師 (80757237)

Co-Investigator(Kenkyū-buntansha) 宮城 重人  東北大学, 大学病院, 准教授 (00420042)
後藤 昌史  東北大学, 医学系研究科, 教授 (50400453)
原 康之  東北大学, 医学系研究科, 非常勤講師 (50636008)
Research Collaborator Hara Yasuyuki  東北大学, 大学病院, 非常勤講師 (50636008)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Keywords線維芽細胞シート被覆肝細胞 / 門脈内移植 / 肝臓実質内移植 / 脾臓実質内移植 / 原始免疫反応 / 自己細胞シート / 肝細胞移植 / 親生体素材シート / 自己線維芽細胞シート / 被覆肝細胞 / 細胞移植 / 門脈圧亢進 / 類洞微小循環 / 移植・再生医療
Outline of Final Research Achievements

Rat hepatocytes were isolated using a modified two-step collagenase perfusion technique and then purified by Percoll density gradient centrifugation. Hepatocytes (1.0 × 107) with a viability exceeding 90% were directly injected into the portal vein (n=8), spleen pulp (n=8), liver parenchyma, and so on, on the analbuminemic rats using a gastight syringe for 60 seconds. Blood samples were taken pre-transplantation and at weeks 2, 4, 6, 8, 10, 12, and 16 after transplantation. The serum albumin levels were quantified using a rat albumin enzyme-linked immunosorbent assay kit.
As a result, the serum albumin levels of the intrasplenic group (pre-transplantation: 7.55±0.65 μg/ml, Week 2: 55.00±21.02 μg/ml, Week 4: 79.88±32.62 μg/ml, Week 6: 105.96±54.46 μg/ml, Week 8: 114.73±58.34 μg/ml, Week 10: 116.11±56.33 μg/ml, Week 12: 122.76±60.85 μg/ml, and Week 16: 133.96±66.03 μg/ml, respectively) were significantly lower than those of the intraportal group

Academic Significance and Societal Importance of the Research Achievements

細胞の大きさで生着率が変わるのではなく個々の細胞の性質で生着率が変わることが分かった点、最も生着効率が高いのは結果的には門脈内肝細胞移植であることが分かった点、肝細胞は線維芽細胞シート被覆により原始免疫反応を回避する効果があり生着率が上がることが分かった点で、学術的意義が高いと考えられる

Report

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

    (18 results)

All 2018 2017 2016

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 4 results) Presentation (8 results) (of which Int'l Joint Research: 6 results)

  • [Journal Article] Cytoprotective Effects of Mesenchymal Stem Cells During Liver Transplantation from Donors After Cardiac Death in Rats.2018

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

      Transplant Proc. 2018 Nov;50(9):2815-2820.

      Volume: 50(9) Issue: 9 Pages: 2815-2820

    • DOI

      10.1016/j.transproceed.2018.02.180

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation Between Splenectomy and Portal Vein Complications in Living Donor Liver Transplantation.2018

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

      Transplant Proc. 2018 Nov;50(9):2611-2613.

      Volume: 50(9) Issue: 9 Pages: 2611-2613

    • DOI

      10.1016/j.transproceed.2018.03.104

    • 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] 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 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [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] Arterial and biliary complications after living donor liver transplantation: a single-center retrospective study and literature review.2018

    • Author(s)
      Miyagi S, Kakizaki Y, Shimizu K, Miyazawa K, Nakanishi W, Hara Y, Tokodai K, Nakanishi C, Kamei T, Ohuchi N, Satomi S.
    • Journal Title

      Surg Today

      Volume: 48(2) Issue: 2 Pages: 131-139

    • DOI

      10.1007/s00595-017-1515-9

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Optimization of Short-Term Hepatocyte Preservation Before Transplantation.2017

    • 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

      Transplant Direct.

      Volume: 19;3(7) Issue: 7 Pages: e176-e176

    • DOI

      10.1097/txd.0000000000000687

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful Simultaneous Pancreas-Kidney Transplantation Using the Injured Pancreas Graft2017

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

      Transplant Proc.

      Volume: 49(10) Issue: 10 Pages: 2315-2317

    • DOI

      10.1016/j.transproceed.2017.10.017

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Resveratrol Prevents Warm Ischemia-Reperfusion Injury in Liver Grafts From Non-Heart-Beating Donor Rats2016

    • Author(s)
      K. Shimizu, S. Miyagi, K. Miyazawa, M. Goto, et al.(total 9)
    • Journal Title

      Transplantation Proceedings

      Volume: 48 Issue: 4 Pages: 1221-25

    • DOI

      10.1016/j.transproceed.2015.11.031

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] The reconstruction of hepatic arteries using extra-anatomical free autografts in living donor liver transplantation2016

    • Author(s)
      Miyagi S, Shimizu K,Miyazawa K, Kakizaki Y, Fujio A, Hara Y, Nakanishi C, Goto H,Kamei T,Kawagishi N, Ohuchi N, and Satomi S.
    • Journal Title

      J Transplant Technol Res

      Volume: 7:2 Issue: 02 Pages: 157-157

    • DOI

      10.4172/2161-0991.1000157

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] The optimization of the hepatocyte surface modification procedures in terms of heparin and apyrase for improving hepatocyte engraftment2018

    • Author(s)
      Hiroyuki Ogasawara1, Yuji Teramura2,3, Takehiro Imura4, Akiko Inagaki4, Yoshikatsu Saito1, Muneyuki Matsumura1, Kengo Fukuoka1, Ibrahim Fathi4, Shigehito Miyagi1, Kristina Nilsson3, Kazuo Ohashi5, Michiaki Unno1, Takashi Kamei1, Susumu Satomi1, Bo Nilsson3, Elisabet Gustafson6, Masafumi Goto1,2
    • Organizer
      27th International Congress of The Transplantation Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A comparison of the transplant efficiency between intraportal and intrasplenic procedures in hepatocyte transplantation2018

    • Author(s)
      Hiroyuki Ogasawara1, Akiko Inagaki2, Takehiro Imura2, Yoshikatsu Saito1, Muneyuki Matsumura1, Kengo Fukuoka1, Ibrahim Fathi2, Shigehito Miyagi1, Kazuo Ohashi3, Michiaki Unno1, Takashi Kamei1, Susumu Satomi1 and Masafumi Goto1,2
    • Organizer
      27th International Congress of The Transplantation Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The risk factors for portal vein thrombosis after living donor liver transplantation in adults2018

    • Author(s)
      Shigehito Miyagi, Chikashi Nakanishi, Yasuyuki Hara, Wataru Nakanishi, Kazuaki Tokodai, Kenji Shimizu, Satomi Uematsu, Hiroyuki Kumata, Yuta Kakizaki, Masafumi Goto, Susumu Satomi, Michiaki Unno and Takashi Kamei
    • Organizer
      27th International Congress of The Transplantation Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Cytoprotective Effects of Mesenchymal Stem Cells on Liver Transplantation from Donors after Cardiac Death2017

    • Author(s)
      Hideaki Sasajima, Shigehito Miyagi, Koji Miyazawa, Kenji Shimizu, Takashi Kamei1, Michiaki Unno1, Susumu Satomi1, and Masafumi Goto
    • Organizer
      15th Congress of the Asian Society of Transplantation (CAST)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of the middle hepatic vein tributaries preserving technique just until graft retrieving on donors' surgical outcomes in living donor liver transplantation2017

    • Author(s)
      Koji Miyazwa, Shigehito Miyagi, Chikashi Nakanishi, Yasuyuki Hara, Kazuaki Tokodai, Wataru Nakanishi
    • Organizer
      15th Congress of the Asian Society of Transplantation (CAST)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肝細胞移植におけるグラフト保存法の至適化2016

    • Author(s)
      福岡健吾,松村宗幸,吉田諭,猪村武弘,稲垣明子,五十嵐康宏, 宮城重人,大橋一夫,絵野沢 伸,大内憲明,里見 進,後藤昌史
    • Organizer
      日本移植学会
    • Place of Presentation
      東京品川 グランドプリンス新高輪
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] 移植前肝細胞評価法としてのADP/ATP assayの有用性に関する検証2016

    • Author(s)
      松村 宗幸1 猪村 武弘2 福岡 健吾1 稲垣 明子2 宮城 重人1 大橋 一夫3 大内 憲明4 里見 進1 後藤 昌史1 2
    • Organizer
      日本移植学会
    • Place of Presentation
      東京品川 グランドプリンス新高輪
    • Year and Date
      2016-09-29
    • Related Report
      2016 Research-status Report
  • [Presentation] The effects of resveratrol on liver transplantation from non-heart-beating donors in pigs.2016

    • Author(s)
      Kenji Shimizu1, Shigehito Miyagi1, Koji Miyazawa1, Kai Maida1, Toshiaki Kashiwadate1,Yasuyuki Hara1, Masafumi Goto1,2, Naoki Kawagishi1, Noriaki Ohuchi1 and Susumu Satomi1
    • Organizer
      国際移植学会
    • Place of Presentation
      HongKong, China
    • Year and Date
      2016-08-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2020-03-30  

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