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Functional liver tissue rebuilding with bile duct structure on heterotopic transplantation

Research Project

Project/Area Number 16K10428
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General surgery
Research InstitutionThe University of Tokushima

Principal Investigator

MORINE Yuji  徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60398021)

Co-Investigator(Kenkyū-buntansha) 池本 哲也  徳島大学, 病院, 特任准教授 (20398019)
齋藤 裕  徳島大学, 病院, 特任助教 (50548675)
居村 暁  徳島大学, 病院, 特任教授 (90380021)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords異所性肝移植 / ADRC / 胆管細胞 / 3次元培養 / 肝細胞 / 肝再生 / 胆管構築
Outline of Final Research Achievements

The purpose of this study was to establish the procedure of functional liver tissue rebuilding with bile duct structure on heterotopic liver tissue transplantation using adipose-derived regenerative cells (ADRC) and 3D culture system.
We demonstrated the protective effect of ADRC for transplant liver function and the differentiation to hepatocyte like cell, but not the ability to differentiate along multiple lineage pathways for other liver component cell from ADRC. Therefore, the pre-induction protocol of ADRC towards cholangiocyte seemed to be necessary before the combined transplantation. Also, 3D culture system indicated the protective effect of primary hepatocyte culture. But, we could not establish the optimal protocol of cholangiocyte differentiation from ADRC, yet. Consequently, while there were some future problems, the possibility of 3D culture system on liver tissue transplantation and the directionality of liver tissue rebuilding approach could be indicated in this study.

Academic Significance and Societal Importance of the Research Achievements

本研究ではADRC・3次元培養システムを活用した異所性肝移植の長期安定化や胆管構築を伴った機能的異所性肝組織再構築の可能性について検討した。残念ながら、ADRCの肝細胞機能維持は確認されたが、胆管細胞分化・組織再構築までの結果を得ることはできず、胆管構造を有する組織再構築には、課題が残ったが、3次元培養システムの可能性や肝組織再構築手法の方向性を示すことはできたと思われる。

Report

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

    (27 results)

All 2019 2018 2017 2016

All Journal Article (13 results) (of which Peer Reviewed: 13 results,  Open Access: 1 results) Presentation (14 results)

  • [Journal Article] The protective effect of epigallocatechin 3-gallate on mouse pancreatic islets via the Nrf2 pathway2019

    • Author(s)
      Wada Yuma、Takata Atsushi、Ikemoto Tetsuya、Morine Yuji、Imura Satoru、Iwahashi Shuichi、Saito Yu、Shimada Mitsuo
    • Journal Title

      Surgery Today

      Volume: Epub ahead of print Issue: 6 Pages: 536-545

    • DOI

      10.1007/s00595-019-1761-0

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A new formula to calculate the resection limit in hepatectomy based on Gd-EOB-DTPA-enhanced magnetic resonance imaging2019

    • Author(s)
      Yamada Shinichiro、Shimada Mitsuo、Morine Yuji、Imura Satoru、Ikemoto Tetsuya、Saito Yu、Takasu Chie、Yoshikawa Masato、Teraoku Hiroki、Yoshimoto Toshiaki
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: 210579-210579

    • DOI

      10.1371/journal.pone.0210579

    • NAID

      120006556317

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration2018

    • Author(s)
      Y Saito, Y Morine, S Iwahashi, T Ikemoto, S Imura, H Yamanaka-Okumura, A Hirayama, T Soga, M Tomita, M Shimada
    • Journal Title

      Ann Gastroenterol Surg

      Volume: - Issue: 3 Pages: 1-8

    • DOI

      10.1002/ags3.12058

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photobiomodulation with red light-emitting diodes accelerates hepatocyte proliferation through reactive oxygen species/extracellular signal-regulated kinase pathway2018

    • Author(s)
      Feng Rui、Morine Yuji、Ikemoto Tetsuya、Imura Satoru、Iwahashi Shuichi、Saito Yu、Shimada Mitsuo
    • Journal Title

      Hepatology Research

      Volume: 48 Issue: 11 Pages: 926-936

    • DOI

      10.1111/hepr.13182

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A New 2-Step Acceleration Protocol Using a Histone Deacetylase Inhibitor to Generate Insulin-Producing Cells From Adipose-Derived Mesenchymal Stem Cells2018

    • Author(s)
      Ikemoto Tetsuya、Feng Rui、Shimada Mitsuo、Saito Yu、Iwahashi Shuichi、Morine Yuji、Imura Satoru
    • Journal Title

      Pancreas

      Volume: 47(4) Issue: 4 Pages: 477-481

    • DOI

      10.1097/mpa.0000000000001017

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment strategy for successful hepatic resection of icteric liver2018

    • Author(s)
      Yada Keigo、Morine Yuji、Ishibashi Hiroki、Mori Hiroki、Shimada Mitsuo
    • Journal Title

      The Journal of Medical Investigation

      Volume: 65 Issue: 1.2 Pages: 37-42

    • DOI

      10.2152/jmi.65.37

    • NAID

      130006575599

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Major liver resection reduces nonprotein respiratory quotient and increases nonesterified fatty acid at postoperative day 14 in patients with hepatocellular carcinoma2018

    • Author(s)
      Wada Shoko、Yamanaka-Okumura Hisami、Katayama Takafumi、Morine Yuji、Imura Satoru、Shimada Mitsuo
    • Journal Title

      Clinical Nutrition ESPEN

      Volume: 23 Pages: 194-199

    • DOI

      10.1016/j.clnesp.2017.10.001

    • NAID

      120006937626

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Treatment strategy for successful hepatic resection of icteric liver.2018

    • Author(s)
      Yada K, Morine Y, Ishibashi H, Mori H, Shimada M.
    • Journal Title

      Journal of Medical Investigation

      Volume: 65 Pages: 37-42

    • NAID

      130006575599

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Accurate Estimation of Functional Liver Volume Using Gd-EOB-DTPA MRI Compared to MDCT/99mTc-SPECT Fusion Imaging2017

    • Author(s)
      Morine Y, Enkhbold C, Imura S, Ikemoto T, Iwahashi S, Saito YU, Yamada S, Utsunomiya T, Shimada M.
    • Journal Title

      Anticancer Research

      Volume: 37 Issue: 10 Pages: 5693-5700

    • DOI

      10.21873/anticanres.12006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mechanism of impairment on liver regeneration in elderly patients: Role of hepatic stellate cell function.2017

    • Author(s)
      Saito Y, Morine Y, Shimada M.
    • Journal Title

      Hepatology Research

      Volume: 印刷中 Issue: 6 Pages: 505-513

    • DOI

      10.1111/hepr.12872

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effective stepwise training and procedure standardization for young surgeons to perform laparoscopic left hepatectomy.2017

    • Author(s)
      Yamada S, Shimada M, Imura S, Morine Y, Ikemoto T, Saito Y, Takasu C, Yoshikawa M, Teraoku H, Yoshimoto T, Takata A.
    • Journal Title

      Surgical Endosopy.

      Volume: 印刷中 Issue: 6 Pages: 2623-2629

    • DOI

      10.1007/s00464-016-5273-3

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Elevated Preoperative Serum CEA Level Is Associated with Poor Prognosis in Patients with Hepatocellular Carcinoma Through the Epithelial-Mesenchymal Transition.2017

    • Author(s)
      Yoshikawa M, Morine Y, Ikemoto T, Imura S, Higashijima J, Iwahashi S, Saito YU, Takasu C, Yamada S, Ishikawa D, Teraoku H, Takata A, Yoshimoto T, Shimada M
    • Journal Title

      Anticancer Res.

      Volume: 37 Issue: 3 Pages: 1169-1175

    • DOI

      10.21873/anticanres.11430

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Role of thrombospondin-1 expression in colorectal liver metastasis and its molecular mechanism2016

    • Author(s)
      H.Teraoku, Y.Morine, T.Ikemoto, Y.Saito, S.Yamada, M.Yoshikawa, C.Takasu, J.Higashijima, S.Imura, M.Shimada
    • Journal Title

      Journal of Hepato-Biliary-Pancreatic Sciences

      Volume: 23 Issue: 9 Pages: 565-573

    • DOI

      10.1002/jhbp.376

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 臨床応用を目指した間葉系幹細胞から創生されるインスリン産生細胞による糖尿病の治療法確立に関する研究2018

    • Author(s)
      池本哲也, 島田光生, 森根裕二, 居村暁, 岩橋衆一, 齋藤裕, 和田佑馬, 寺奥大貴, 太田昇吾
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Epigallocatechin-3-gallateはNrf2を介して 膵島保護作用を有する2018

    • Author(s)
      岩橋衆一, 島田光生, 森根裕二, 居村暁, 池本哲也, 齋藤裕, 和田佑馬, 寺奥大貴
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝予備能を加味したOne Stop Shop SimulationとMixed realityによる新たなNavigation2018

    • Author(s)
      齋藤裕, 居村暁, 森根裕二, 池本哲也, 岩橋衆一, 寺奥大貴, 杉本真樹, 島田光生
    • Organizer
      第118回日本外科学会定期学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 発光ダイオード(LED)の波長強度可変装置による肝細胞保護に関する研究2018

    • Author(s)
      岩橋衆一, 島田光生, 居村暁, 森根裕二, 池本哲也, 齋藤裕, 寺奥大貴
    • Organizer
      第36回日本肝移植研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Nrf2経路によるEGCGの膵島保護効果2018

    • Author(s)
      和田佑馬, 池本哲也, 森根裕二, 岩橋衆一, 齋藤裕, 山田眞一郎, 居村暁, 島田光生
    • Organizer
      第54回日本移植学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 肝細胞に対するROS/ ERK pathwayを介した赤色LED光の細胞増殖促進効果2017

    • Author(s)
      吉川雅登, Rui Feng, 森根裕二, 居村暁, 池本哲也, 岩橋衆一, 齋藤裕, 石川大地, 髙田厚史, 良元俊昭, 高須千絵, 東島潤, 島田光生
    • Organizer
      第117回日本外科学会定期学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] メタボローム解析を用いた肝切除後代謝物解析と肝再生因子の解明2017

    • Author(s)
      齋藤裕, 奥村仙示, 森根裕二, 平山明由, 良元俊昭, 吉川雅登, 岩橋衆一, 池本哲也, 居村暁, 島田光生
    • Organizer
      第54回日本外科代謝栄養学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] One stop shopを目指したEOB-MRIによる部分肝機能評価2017

    • Author(s)
      岩橋衆一, 島田光生, 森根裕二, 居村暁, 池本哲也, 齋藤裕, 吉川雅登, 良元俊昭, 髙田厚史
    • Organizer
      第72回日本消化器外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] pigallocatechin-3-gallate (EGCG)によるNrf2-Keap1制御系を介した膵島保護作用に関する検討2017

    • Author(s)
      髙田厚史, 池本哲也, 岩橋衆一, 齋藤裕, 森根裕二, 居村暁, 島田光生
    • Organizer
      第72回日本消化器外科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] 膵島移植に対するブレイクスルーとしてのAdipose tissue derived stem cellsからの効果的Insulin-producing cells創生2017

    • Author(s)
      池本哲也, 島田光生, 居村暁, 森根裕二, 岩橋衆一, 齋藤裕, 寺奥大貴
    • Organizer
      第53回日本移植学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] EOB-MRI is useful for `one stop shop` modality based on functional liver volume2017

    • Author(s)
      Teraoku H, Shimada M, Morine Y, Imura S, Ikemoto T, Iwahashi S, Saito Y, Yoshikawa M
    • Organizer
      第29回日本肝胆膵外科学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肝細胞に対するROS/ ERK pathwayを介した赤色LED光の細胞増殖促進効果2016

    • Author(s)
      吉川雅登,Feng Rui,森根裕二,居村暁,池本哲也,東島潤,西正暁,岩橋衆一,齋藤裕,高須千絵,石川大地,髙田厚史,良元俊昭,島田光生
    • Organizer
      第46回日本創傷治癒学会
    • Place of Presentation
      東京大学伊藤国際学術研究センター(東京都文京区)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 脂肪由来幹細胞によるInsulin-producing cell作成における新規分化誘導方2016

    • Author(s)
      池本哲也, 島田光生, 居村暁, 森根裕二, 岩橋衆一, 齋藤裕, 吉川雅登, 良元俊昭
    • Organizer
      第52回日本移植学会総会
    • Place of Presentation
      グランドプリンスホテル新高輪(東京都港区)
    • Year and Date
      2016-10-01
    • Related Report
      2016 Research-status Report
  • [Presentation] HDAC阻害剤は脂肪由来幹細胞からインスリン分泌細胞への分化誘導を促進する2016

    • Author(s)
      齋藤裕, 良元俊昭, 髙田厚史, 吉川雅登, 寺奥大貴, 山田眞一郎, 池本哲也, 森根裕二, 居村暁, 島田光生.
    • Organizer
      第116回日本外科学会定期学術集会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-04-14
    • Related Report
      2016 Research-status Report

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

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