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The development of liver regeneration therapy with higher therapeutic effects on liver cirrhosis using a middle-large size liver cirrhosis model.

Research Project

Project/Area Number 17H04162
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionYamaguchi University

Principal Investigator

SAKAIDA Isao  山口大学, 大学院医学系研究科, 教授 (80263763)

Co-Investigator(Kenkyū-buntansha) 藤澤 浩一  山口大学, 大学院医学系研究科, 助教 (00448284)
高見 太郎  山口大学, 大学院医学系研究科, 講師 (60511251)
松本 俊彦  山口大学, 大学院医学系研究科, 助教 (70634723)
山本 直樹  山口大学, 大学教育機構, 准教授 (90448283)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Keywords肝硬変症 / 再生療法 / 間葉系幹細胞 / 骨髄間葉系幹細胞 / 肝臓再生 / 骨髄細胞 / 移植・再生医療
Outline of Final Research Achievements

To develop liver regeneration therapy with higher therapeutic effects using cultured autologous bone marrow derived mesenchymal stem cells (BM-MSCs) on decompensated liver cirrhosis, we have been conducting translational research. In this study, we have revealed follows; 1) the hepatic arterial infusion of cryopreserved cultured autologous BM-MSCs have equivalent effects on liver cirrhosis model, 2) although BM-MSCs have an immunosuppressive effect, the frequent infusion of cultured autologous BM-MSCs did not accelerate the early stages of hepatocarcinogenesis in highly oncogenic liver cirrhotic murine model, 3) using luciferase-positive BM-MSCs, direct infusion into the liver via portal vein was more effective than peripheral intravenous infusion, 4) the infusion of BM-MSCs showed effects on liver fibrosis and steatosis in a modified murine non-alcoholic steatohepatitis (NASH) model. Therefore, we will develop the next liver regeneration therapy based on these findings.

Academic Significance and Societal Importance of the Research Achievements

これまで非代償性肝硬変に対する抗線維化や再生療法の開発が多く実施されているが、肝移植が根治療法であることに変わりはない。これまで我々は「培養自己骨髄間葉系幹細胞を用いた低侵襲肝臓再生療法」を開発し、安全性評価目的の臨床研究を実施している。今回の研究成果は、より治療効果を高めた肝臓再生療法の開発につながることから、肝硬変治療の実現に寄与するだけでなく、他の臓器線維症にも波及効果がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (45 results)

All 2020 2019 2018 2017 Other

All Journal Article (17 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 17 results,  Open Access: 14 results) Presentation (23 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (5 results)

  • [Journal Article] Bone marrow-derived humoral factors suppress oxidative phosphorylation, upregulate TSG-6, and improve therapeutic effects on liver injury of mesenchymal stem cells2020

    • Author(s)
      Miyaji Takashi、Takami Taro、Fujisawa Koichi、Matsumoto Toshihiko、Yamamoto Naoki、Sakaida Isao
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 66 Issue: 3 Pages: 213-223

    • DOI

      10.3164/jcbn.19-125

    • NAID

      130007839286

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the Effects of Cultured Bone Marrow Mesenchymal Stem Cell Infusion on Hepatocarcinogenesis in Hepatocarcinogenic Mice With Liver Cirrhosis.2019

    • Author(s)
      Matsuura K, Takami T, Maeda M, Hisanaga T, Fujisawa K, Saeki I, Matsumoto T, Hidaka I, Yamamoto N, Sakaida I.
    • Journal Title

      Transplant Proc.

      Volume: 51(3) Issue: 3 Pages: 925-935

    • DOI

      10.1016/j.transproceed.2019.03.011

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Canine Liver Fibrosis Model to Assess the Functions of Infused Autologous Bone Marrow-Derived Cells.2019

    • Author(s)
      Takami T, Tani K, Taura Y, Sakaida I.
    • Journal Title

      Methods Mol Biol.

      Volume: 1905 Pages: 201-209

    • DOI

      10.1007/978-1-4939-8961-4_18

    • ISBN
      9781493989607, 9781493989614
    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Liver regeneration therapy through the hepatic artery-infusion of cultured bone marrow cells in a canine liver fibrosis model.2019

    • Author(s)
      Nishimura T, Takami T, Sasaki R, Aibe Y, Matsuda T, Fujisawa K, Matsumoto T, Yamamoto N, Tani K, Taura Y, Sakaida I.
    • Journal Title

      PLoS One.

      Volume: 14(1) Issue: 1 Pages: 234-244

    • DOI

      10.1371/journal.pone.0210588

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Usefulness of Adult Medaka Fish as a Model for the Evaluation of Alcoholic Fatty Liver.2019

    • Author(s)
      Fujisawa K, Takami T, Nagatomo T, Fukui Y, Hoshida H, Saeki I, Matsumoto T, Hidaka I, Yamamoto N, Sakaida I.
    • Journal Title

      Alcohol.

      Volume: 77 Pages: 147-154

    • DOI

      10.1016/j.alcohol.2019.01.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Liver stiffness measured by transient elastography as predictor of prognoses following portosystemic shunt occlusion.2019

    • Author(s)
      Ishikawa T, Sasaki R, Nishimura T, Matsuda T, Maeda M, Iwamoto T, Saeki I, Hidaka I, Takami T, Sakaida I.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: 34(1) Issue: 1 Pages: 215-223

    • DOI

      10.1111/jgh.14410

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] No Muscle Depletion with High Visceral Fat as a Novel Beneficial Biomarker of Sorafenib for Hepatocellular Carcinoma.2018

    • Author(s)
      Saeki I, Yamasaki T, Maeda M, Kawano R, Hisanaga T, Iwamoto T, Matsumoto T, Hidaka I, Ishikawa T, Takami T, Sakaida I.
    • Journal Title

      Liver Cancer.

      Volume: 7(4) Issue: 4 Pages: 359-371

    • DOI

      10.1159/000487858

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of tolvaptan non-responders and outcomes of tolvaptan treatment of ascites.2018

    • Author(s)
      Iwamoto T, Maeda M, Saeki I, Hidaka I, Tajima K, Ishikawa T, Takami T, Sakaida I.
    • Journal Title

      J Gastroenterol Hepatol.

      Volume: - Issue: 7 Pages: 1231-1235

    • DOI

      10.1111/jgh.14524

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treatment strategies for advanced hepatocellular carcinoma: Sorafenib vs hepatic arterial infusion chemotherapy.2018

    • Author(s)
      Saeki I, Yamasaki T, Maeda M, Hisanaga T, Iwamoto T, Fujisawa K, Matsumoto T, Hidaka I, Marumoto Y, Ishikawa T, Yamamoto N, Suehiro Y, Takami T, Sakaida I.
    • Journal Title

      World J Hepatol.

      Volume: 10(9) Issue: 9 Pages: 571-584

    • DOI

      10.4254/wjh.v10.i9.571

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of high-fat-diet-induced fatty liver in medaka.2018

    • Author(s)
      Fujisawa K, Takami T, Fukui Y, Nagatomo T, Saeki I, Matsumoto T, Hidaka I, Yamamoto N, Okamoto T, Furutani-Seiki M, Sakaida I
    • Journal Title

      Biol Open.

      Volume: 7(11) Pages: 341-347

    • DOI

      10.1242/bio.031534

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Deferasirox, an oral iron chelator, with gemcitabine synergistically inhibits pancreatic cancer cell growth in vitro and in vivo.2018

    • Author(s)
      Shinoda S, Kaino S, Amano S, Harima H, Matsumoto T, Fujisawa K, Takami T, Yamamoto N, Yamasaki T, Sakaida I.
    • Journal Title

      Oncotarget.

      Volume: 9(47) Issue: 47 Pages: 28434-28444

    • DOI

      10.18632/oncotarget.25421

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of patients with hepatic encephalopathy and those with gastric varices before and after balloon-occluded retrograde transvenous obliteration.2018

    • Author(s)
      Ishikawa T, Sasaki R, Nishimura T, Matsuda T, Maeda M, Iwamoto T, Saeki I, Hidaka I, Takami T, Sakaida I.
    • Journal Title

      Hepatol Res.

      Volume: 48(12) Issue: 12 Pages: 1020-1030

    • DOI

      10.1111/hepr.13199

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blood free-circulating DNA testing by highly sensitive methylation assay to diagnose colorectal neoplasias.2018

    • Author(s)
      Suehiro Y, Hashimoto S, Higaki S, Fujii I, Suzuki C, Hoshida T, Matsumoto T, Yamaoka Y, Takami T, Sakaida I, Yamasaki T.
    • Journal Title

      Oncotarget.

      Volume: 9(24) Issue: 24 Pages: 16974-16987

    • DOI

      10.18632/oncotarget.24768

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the effects of ascorbic acid on metabolism of human mesenchymal stem cells.2018

    • Author(s)
      Fujisawa K, Hara K, Takami T, Okada S, Matsumoto T, Yamamoto N, Sakaida I.
    • Journal Title

      Stem Cell Res Ther.

      Volume: 9(1) Issue: 1 Pages: 93-93

    • DOI

      10.1186/s13287-018-0825-1

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of Metabolomic Changes in Mesenchymal Stem Cells on Treatment with Desferrioxamine as a Hypoxia Mimetic Compared to Hypoxic Conditions.2018

    • Author(s)
      Fujisawa K, Takami T, Okada S, Hara K, Matsumoto T, Yamamoto N, Yamasaki T, Sakaida I.
    • Journal Title

      Stem Cells.

      Volume: 印刷中

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Profiling of the circadian metabolome in thioacetamide-induced liver cirrhosis in mice.2017

    • Author(s)
      Fujisawa K, Takami T, Matsumoto T, Yamamoto N, Sakaida I.
    • Journal Title

      Hepatol Commun.

      Volume: 1(7) Issue: 7 Pages: 704-718

    • DOI

      10.1002/hep4.1075

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A canine liver fibrosis model to develop a therapy for liver cirrhosis using cultured bone marrow-derived cells.2017

    • Author(s)
      Matsuda T, Takami T, Sasaki R, Nishimura T, Aibe Y, Paredes BD, Quintanilha LF, Matsumoto T, Ishikawa T, Yamamoto N, Tani K, Terai S, Taura Y, Sakaida I.
    • Journal Title

      Hepatology Communications

      Volume: 1 Issue: 7 Pages: 691-703

    • DOI

      10.1002/hep4.1071

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Resolution of liver fibrosis by autologous bone marrow cell infusion therapy can improve liver function2019

    • Author(s)
      Takami Taro
    • Organizer
      中日先進医療と新薬研究サミット及び成果実業化大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 培養自己骨髄間葉系幹細胞を用いた肝臓再生療法におけるエクソソーム(細胞外小胞)2019

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      第26回肝細胞研究会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 培養自己骨髄間葉系幹細胞肝動脈投与による自己完結型肝硬変再生療法の開発と機序解明2019

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      日本消化器病学会週間
    • Related Report
      2019 Annual Research Report
  • [Presentation] 非代償性肝硬変に対する自己完結型肝硬変再生療法の開発2019

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      第43回日本肝臓学会西部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 非代償性肝硬変症に対する自己骨髄間葉系幹細胞を用いた再生療法の開発と展望2019

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Our developed liver regeneration therapy using autologous bone marrow derived mesenchymal stem cells for decompensated liver cirrhotic patients2019

    • Author(s)
      Takami Taro, Matsumoto Toshihiko, Sakaida Isao
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Functional analysis of microRNA142-3p in human hepatic stellate cells to develop anti-fibrotic nucleic acid therapeutics for liver cirrhosis2019

    • Author(s)
      Matsumoto Toshihiko, Takami Taro, Yamasaki Takahiro, Sakaida Isao
    • Organizer
      JSH International Liver Conference 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨髄間葉系幹細胞を用いた肝臓再生療法に対する microRNAを用いた補助療法の開発2019

    • Author(s)
      松本 俊彦、藤澤 浩一、高見 太郎、山本 直樹、末広 寛、山﨑 隆弘、坂井田 功
    • Organizer
      第51回日本臨床形態分子学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] microRNAの特性利用による抗線維化核酸医薬品の開発に向けた基礎検討2019

    • Author(s)
      松本 俊彦、藤澤 浩一、高見 太郎、山本 直樹、山崎 隆弘、坂井田 功
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 核酸医薬品の開発を目指した肝星細胞におけるmiR142-3pの機能解析2019

    • Author(s)
      松本 俊彦、高見 太郎、坂井田 功
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Direct infusion of cultured autologous bone marrow-derived mesenchymal stem cells offers higher therapeutic efficacy than conventional peripheral infusion in liver fibrosis animal models2018

    • Author(s)
      Takami T, Sasaki R, Nishimura T, Matsuda T, Fujisawa K, Matsumoto T, Yamamoto N, Sakaida I.
    • Organizer
      6th Annual Midwest Conference on Cell Therapy and Regenerative Medicine
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 抗線維化療法としての自己骨髄細胞を用いた非代償性肝硬変症に対する再生療法の臨床実施と展開2018

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      第54回日本肝臓学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非代償性肝硬変症に対する自己骨髄由来細胞を用いた再生療法の臨床実施2018

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      第53回日本アルコール・アディクション医学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非代償性肝硬変症に対する培養自己骨髄間葉系幹細胞肝動脈投与療法の開発2018

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      JDDW 2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非代償性肝硬変に対する自己骨髄由来細胞を用いた再生療法の臨床実施2018

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      第104回日本消化器病学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 非代償性肝硬変に対する自己骨髄由来細胞を用いた肝臓再生療法の臨床実施2018

    • Author(s)
      高見 太郎、松本 俊彦、久永 拓郎、藤澤 浩一、石川 剛、坂井田 功
    • Organizer
      第115回日本内科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 当科における非代償性肝硬変症に対する培養自己骨髄間葉系幹細胞を用いた再生治療2018

    • Author(s)
      高見 太郎、野島 順三、坂井田 功
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Our liver regeneration therapies using autologous bone marrow-derived cells for decompensated liver cirrhosis2017

    • Author(s)
      Taro Takami, and Isao Sakaida
    • Organizer
      第54回日本消化器免疫学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The development of liver regeneration therapies using autologous bone marrow cells for liver cirrhosis2017

    • Author(s)
      Taro Takami, and Isao Sakaida
    • Organizer
      ConBio2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝硬変症に対する自己骨髄細胞による再生療法の開発状況と展望2017

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      第103回日本消化器病学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 非代償性肝硬変症に対する自己骨髄細胞を用いた再生療法の臨床実施と機序解明2017

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 当科における非代償性肝硬変に対する自己骨髄細胞を用いた再生療法2017

    • Author(s)
      高見 太郎、松本 俊彦、坂井田 功
    • Organizer
      JDDW2017
    • Related Report
      2017 Annual Research Report
  • [Presentation] 培養自己骨髄間葉系幹細胞を用いた肝臓再生療法における細胞投与経路の検討2017

    • Author(s)
      高見 太郎、坂井田 功
    • Organizer
      第114回日本内科学会総会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 山口大学研究推進機構 再生・細胞治療研究センター

    • URL

      http://kenkyu.yamaguchi-u.ac.jp/rcasi/saisei.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 山口大学医学部医学科 肝臓再生基盤学

    • URL

      http://www.med.yamaguchi-u.ac.jp/medicine/chair/kifu_03.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 山口大学医学部医学科 消化器内科学

    • URL

      https://www.ichinai-yamaguchi.jp/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 山口大学研究推進機構 再生・細胞治療研究センター

    • URL

      http://rcasi.kenkyu.yamaguchi-u.ac.jp/saisei.php

    • Related Report
      2018 Annual Research Report
  • [Remarks] 非代償性肝硬変患者に対する培養自己骨髄細胞肝動脈投与療法について

    • URL

      http://www.hosp.yamaguchi-u.ac.jp/news/news/post_252.html

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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