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Development of a low-invasive, high-efficient liver regeneration therapy by infusion of cultured bone marrow mesenchymal stem cells combined with interventional radiology

Research Project

Project/Area Number 17K10441
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionYamaguchi University

Principal Investigator

ISHIKAWA TSUYOSHI  山口大学, 大学院医学系研究科, 講師 (20569305)

Co-Investigator(Kenkyū-buntansha) 岩本 拓也  山口大学, 大学院医学系研究科, 助教 (80634716)
Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsインターベンショナルラジオロジー / 門脈圧亢進症 / 肝硬変症 / 肝再生
Outline of Final Research Achievements

The present study demonstrated effects of partial splenic embolization and cultured bone marrow mesenchymal stem cell infusion on thrombocytopenia due to hypersplenism and liver dysfunction induced by hepatic decompensation, respectively, in canine cirrhosis model, which were similar to those in human cirrhosis model. In addition, our study suggested that infusion of cultured bone marrow mesenchymal stem cells via hepatic artery after partial splenic embolization would be a low-invasive, high-efficient liver regeneration therapy for decompensated liver cirrhosis.

Academic Significance and Societal Importance of the Research Achievements

本研究では、基礎(イヌ)・臨床(ヒト)の両面から、「部分的脾動脈塞栓術」施行後に培養自己骨髄間葉系幹細胞を「経肝動脈投与」することの安全性と有効性が明らかとなった。
非代償性肝硬変に対する唯一無二の根治療法は「肝移植」であるが、本邦においては脳死肝移植のみならず生体肝移植に対するハードルは依然として高く、手術侵襲・免疫拒絶・ドナー不足など問題は今なお山積みである。「IVR併用・培養骨髄由来間葉系幹細胞投与による肝臓再生療法」が、肝移植への橋渡し治療あるいはその代替療法として近い将来実用化されることを目標に掲げ、本研究成果を基盤とした更なる追加研究を推進していく。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (30 results)

All 2021 2020 2019 2018 2017

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (21 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification2021

    • Author(s)
      Ishikawa Tsuyoshi、Sasaki Ryo、Nishimura Tatsuro、Matsuda Takashi、Iwamoto Takuya、Saeki Issei、Hidaka Isao、Takami Taro、Sakaida Isao
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 9 Pages: 1331-1342

    • DOI

      10.2169/internalmedicine.6267-20

    • NAID

      130008033267

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-05-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Splenic non-infarction volume determines a clinically significant hepatic venous pressure gradient response to partial splenic embolization in patients with cirrhosis and hypersplenism2021

    • Author(s)
      Ishikawa Tsuyoshi、Sasaki Ryo、Nishimura Tatsuro、Matsuda Takashi、Iwamoto Takuya、Saeki Issei、Hidaka Isao、Takami Taro、Sakaida Isao
    • Journal Title

      Journal of Gastroenterology

      Volume: 56 Issue: 4 Pages: 382-394

    • DOI

      10.1007/s00535-021-01762-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Trans-portal hepatic infusion of cultured bone marrow-derived mesenchymal stem cells in a steatohepatitis murine model2020

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

      Journal of Clinical Biochemistry and Nutrition

      Volume: 67 Issue: 3 Pages: 274-282

    • DOI

      10.3164/jcbn.20-88

    • NAID

      130007934155

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Improved Hepatic Reserve and Fibrosis in a Case of “Portal-Systemic Liver Failure” by Portosystemic Shunt Occlusion2020

    • Author(s)
      Ishikawa Tsuyoshi、Sasaki Ryo、Nishimura Tatsuro、Iwamoto Takuya、Takami Taro、Yamasaki Takahiro、Sakaida Isao
    • Journal Title

      American Journal of Case Reports

      Volume: 21

    • DOI

      10.12659/ajcr.921236

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel Therapeutic Strategy Using Interventional Radiology (IVR) for Hepatitis C Virus (HCV)-Related Decompensated Liver Cirrhosis: A Case Report2019

    • Author(s)
      Iwamoto Takuya、Saeki Issei、Hidaka Isao、Ishikawa Tsuyoshi、Takami Taro、Sakaida Isao
    • Journal Title

      American Journal of Case Reports

      Volume: 20 Pages: 1699-1704

    • DOI

      10.12659/ajcr.919240

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel therapeutic strategy for esophageal varices using endoscopic treatment combined with splenic artery embolization according to the Child-Pugh classification2019

    • Author(s)
      Ishikawa Tsuyoshi、Sasaki Ryo、Nishimura Tatsuro、Aibe Yuki、Saeki Issei、Iwamoto Takuya、Hidaka Isao、Takami Taro、Sakaida Isao
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 9 Pages: e0223153-e0223153

    • DOI

      10.1371/journal.pone.0223153

    • Related Report
      2019 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status Report
    • Peer Reviewed
  • [Journal Article] Plasma Glucose Level Is Predictive of Serum Ammonia Level After Retrograde Occlusion of Portosystemic Shunts2017

    • Author(s)
      Ishikawa T, Aibe Y, Matsuda T, Iwamoto T, Takami T, Sakaida I
    • Journal Title

      American Journal of Roentgenology

      Volume: 209 Issue: 3 Pages: W169-W176

    • DOI

      10.2214/ajr.16.17307

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 「HVPG response」の観点から見た部分的脾動脈塞栓術の有用性2020

    • Author(s)
      石川 剛、高見太郎、坂井田 功
    • Organizer
      JDDW2020
    • Related Report
      2020 Annual Research Report
  • [Presentation] HVPGを用いてPSEによる門脈圧降下作用を再考する2020

    • Author(s)
      石川 剛、佐々木 嶺、松田崇史、坂井田 功
    • Organizer
      第27回日本門脈圧亢進症学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 非代償性肝硬変に対する部分的脾動脈塞栓術は是か非か~有効性と安全性の観点より~2020

    • Author(s)
      石川 剛、岩本拓也、坂井田 功
    • Organizer
      第56回日本肝臓学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 術前血糖コントロールは、高アンモニア血症に対するBRTOの治療効果を増強する。2019

    • Author(s)
      石川 剛、岩本拓也、坂井田 功
    • Organizer
      第105回日本消化器病学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Therapeutic Strategy for Prevention of a Recurrence of Esophageal Varices after Endoscopic Treatments2019

    • Author(s)
      石川 剛、岩本拓也、坂井田 功
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Gastrointestinal Bleeding and Acute-on-Chronic Liver Failure2019

    • Author(s)
      石川 剛、岩本拓也、坂井田 功
    • Organizer
      第55回日本肝臓学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] BRTO後の予後予測因子に関する統計解析2019

    • Author(s)
      石川 剛、岩本拓也、坂井田 功
    • Organizer
      第26回日本門脈圧亢進症学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] PSEによる肝血行動態の変化が肝予備能に及ぼす影響~Child-Pugh分類別検討~2019

    • Author(s)
      石川 剛、岩本拓也、坂井田 功
    • Organizer
      第26回日本門脈圧亢進症学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] Liver Stiffness Measured by Transient Elastography is Predictive of the Prognosis following Portosystemic Shunt Occlusion in Patients with Portal Hypertension2019

    • Author(s)
      Tsuyoshi Ishikawa, Ryo Sasaki, Tatsuro Nishimura, Takuya Iwamoto, Taro Takami, Isao Sakaida
    • Organizer
      JSH International Liver Conference 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Portosystemic Shunt Syndromeに対するB-RTOの有効性に関する検討2018

    • Author(s)
      石川 剛、佐々木 嶺、西村 達朗、松田 崇史、岩本 拓也、高見 太郎、坂井田 功
    • Organizer
      第104回 日本消化器病学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 術前肝硬度測定はBRTO後の生命予後を予測し得る2018

    • Author(s)
      石川 剛、高見 太郎、坂井田 功
    • Organizer
      第54回 日本肝臓学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 術前肝硬度測定はB-RTOによるMELD-Naスコア改善を予測し得る2018

    • Author(s)
      石川 剛、岩本 拓也、坂井田 功
    • Organizer
      第25回 日本門脈圧亢進症学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] B-RTOの補助療法としてのPSEの有用性2018

    • Author(s)
      石川 剛、岩本 拓也、坂井田 功
    • Organizer
      第25回 日本門脈圧亢進症学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Liver Stiffness Measured by Transient Elastography is Predictive of the Prognosis following Portosystemic Shunt Occlusion in Patients with Portal Hypertension2018

    • Author(s)
      Tsuyoshi Ishikawa, Ryo Sasaki, Tatsuro Nishimura, Takuya Iwamoto, Taro Takami, Isao Sakaida
    • Organizer
      The Liver Meeting 2018, AASLD
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of hepatic arterial buffer response induced by partial splenic embolization on hepatic function in cirrhotic patients by Child-Pugh classification2018

    • Author(s)
      Tsuyoshi Ishikawa, Ryo Sasaki, Tatsuro Nishimura, Takuya Iwamoto, Taro Takami, Isao Sakaida
    • Organizer
      The Liver Meeting 2018, AASLD
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] B-RTOによるMELD-Naスコア改善の術前予測因子に関する統計学的検討2018

    • Author(s)
      石川 剛、高見 太郎、坂井田 功
    • Organizer
      第42回 日本肝臓学会東部会
    • Related Report
      2018 Research-status Report
  • [Presentation] 部分的脾動脈塞栓術による肝血行動態の変化が肝機能に及ぼす影響~脾臓摘出術との比較~2017

    • Author(s)
      石川 剛、佐々木 嶺、西村 達朗、相部 祐希、松田 崇史、岩本 拓也、高見太郎、坂井田 功
    • Organizer
      第103回日本消化器病学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] B-RTOによるMELD-Naスコア改善に寄与する術前因子の検討2017

    • Author(s)
      石川剛、佐々木嶺、西村達朗、相部祐希、松田崇史、岩本拓也、高見太郎、坂井田功
    • Organizer
      第53回日本肝臓学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Portosystemic Shunt Syndromeに対するB-RTOの有効性に関する統計学的検討2017

    • Author(s)
      石川 剛、岩本拓也、坂井田 功
    • Organizer
      第24回日本門脈圧亢進症学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] Embolization of splenic artery in combination with occlusion of portosystemic shunts has potential to improve hepatic function and extend prognosis in decompensated liver cirrhosis with portal hypertension2017

    • Author(s)
      Tsuyoshi Ishikawa, Ryo Sasaki, Tatsuro Nishimura, Takashi Matsuda, Takuya Iwamoto, Taro Takami, Isao Sakaida
    • Organizer
      The Liver Meeting 2017, AASLD
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Preoperative Liver Stiffness Predicts an Improvement in Vital Prognosis by Occlusion of Portosystemic Shunts in Portal Hypertensive Patients2017

    • Author(s)
      Tsuyoshi Ishikawa, Ryo Sasaki, Tatsuro Nishimura, Takashi Matsuda, Takuya Iwamoto, Taro Takami, Isao Sakaida
    • Organizer
      The Liver Meeting 2017, AASLD
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2022-01-27  

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