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The development research of liver regeneration therapy used bone marrow drived liver repaired cell

Research Project

Project/Area Number 20H03663
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionYamaguchi University

Principal Investigator

SAKAIDA Isao  山口大学, その他部局等, 名誉教授 (80263763)

Co-Investigator(Kenkyū-buntansha) 山本 直樹  山口大学, 教育・学生支援機構, 教授 (90448283)
高見 太郎  山口大学, 大学院医学系研究科, 教授 (60511251)
松本 俊彦  山口大学, 大学院医学系研究科, 講師 (70634723)
藤澤 浩一  産業医科大学, 産業生態科学研究所, 教授 (00448284)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2022: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2021: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2020: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywords再生医療 / 間葉系幹細胞 / 骨髄細胞 / 肝線維化 / 肝脂肪化 / 電子顕微鏡 / 肝硬変 / 肝硬変症 / 肝再生
Outline of Research at the Start

進行した肝硬変症に対する根治療法は肝移植であるが、ドナー不足や手術侵襲、医療経済面等の問題で十分には普及していないため、肝臓再生療法の開発は社会的にも求められている。そこで我々は、マウス肝硬変モデルを用いて投与した骨髄由来間葉系細胞(MSC)と肝臓構成細胞の細胞間相互作用に着目して肝臓再生メカニズムを解明することにより、現在我々が臨床実施している肝臓再生療法をより効果的なものとする。

Outline of Final Research Achievements

Currently, the only curative therapy for refractory cirrhosis is liver transplantation, and the development of new cirrhosis treatment and liver regeneration therapy is an urgent social need. In our previous research, we found that bone marrow cells improved liver fibrosis, that liver repair cells exist in bone marrow cells, and that cultured bone marrow-derived mesenchymal cells (MSCs) improved liver function and liver fibrosis, and we have begun clinical research on these findings. In this study, using these cultured bone marrow-derived mesenchymal cells (MSCs) and non-cultured bone marrow cells, we found that there are two types of liver repair cells in bone marrow-derived liver repair cells and clarified not only the effect of liver repair cells in suppressing liver fibrosis but also the effect of liver repair cells in suppressing liver adipogenesis. These results provide information that can be efficiently developed for ongoing clinical research on liver regeneration therapy.

Academic Significance and Societal Importance of the Research Achievements

我々が行った自己骨髄細胞投与療法の臨床研究では、肝硬変患者は高齢な方が多く、既に肝臓の脂肪化や動脈硬化の進行した症例が多く、肝臓内の脂肪化や体内の動脈硬化の進行例での投与された自己骨髄由来肝臓修復細胞の動態や治療における役割は未だ不明であり、まだ解明されてない課題点が多い。
今回の基礎研究の成果は、副作用のない安全性も確立している自己骨髄細胞による肝臓再生療法の臨床研究の発展に寄与すると考える。またその解析成果から自己骨髄細胞中から重要で有効な肝臓修復細胞を同定し、保存培養可能な方法を確立することが可能となれば、さらに効率的な方法での再生療法へと発展させるための情報を獲得できると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (28 results)

All 2022 2021 2020 Other

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

  • [Journal Article] Adenylate Kinase Isozyme 3 Regulates Mitochondrial Energy Metabolism and Knockout Alters HeLa Cell Metabolism2022

    • Author(s)
      Fujisawa Koichi、Wakazaki Maina、Matsuzaki Aya、Matsumoto Toshihiko、Yamamoto Naoki、Noma Takafumi、Takami Taro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 8 Pages: 4316-4319

    • DOI

      10.3390/ijms23084316

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] An iron chelation-based combinatorial anticancer therapy comprising deferoxamine and a lactate excretion inhibitor inhibits the proliferation of cancer cells2022

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

      Cancer Metabolism

      Volume: 10 Issue: 1 Pages: 8-16

    • DOI

      10.1186/s40170-022-00284-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the Effects of Microgravity on Activated Primary Human Hepatic Stellate Cells2022

    • Author(s)
      Fujisawa Koichi、Nishimura Yuto、Sakuragi Akino、Duponselle Jolien、Matsumoto Toshihiko、Yamamoto Naoki、Murata Tomoaki、Sakaida Isao、Takami Taro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 13 Pages: 7429-7429

    • DOI

      10.3390/ijms23137429

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of DNA Damage Response via the Ccndbp1-Atm-Chk2 Pathway in Mice with Dextran-Sodium-Sulfate-Induced Colitis2022

    • Author(s)
      Horigome R, Kamimura K, Niwa Y, Ogawa K, Mizuno KI, Fujisawa K, Yamamoto N, Takami T, Sugano T, Sakamaki A, Kamimura H, Takamura M, Terai S.
    • Journal Title

      J Clin Med.

      Volume: 11(13) Issue: 13 Pages: 3674-3680

    • DOI

      10.3390/jcm11133674

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cyclin D1 Binding Protein 1 Responds to DNA Damage through the ATM / CHK2 Pathway2022

    • Author(s)
      Niwa Yusuke、Kamimura Kenya、Ogawa K、Oda C、Tanaka Y、Horigome R、Ohtsuka M、Miura H、Fujisawa Koichi、Yamamoto Naoki、Takami Taro、Okuda Shujiro、Ko Masayoshi、Owaki Takashi、Kimura Atsushi、Shibata Osamu、Morita Shinichi、Sakai N、Abe H、Yokoo T、Sakamaki A、Kamimura H、Terai S
    • Journal Title

      Journal of Clinical Medicine

      Volume: 11 Issue: 3 Pages: 851-851

    • DOI

      10.3390/jcm11030851

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of two primer-probe sets of Fusobacterium nucleatum using droplet digital polymerase chain reaction for the detection of colorectal neoplasia from faecal samples2022

    • Author(s)
      Yamaoka Y, Sasai M, Suehiro Y, Hashimoto S, Goto A, Yamamoto N, Suzuki N, Higaki S, Fujii I, Suzuki C, Matsumoto T, Hoshida T, Koga M, Tsutsumi T, Lim LA, Matsubara Y, Tomochika S, Yoshida S, Hazama S, Yotsuyanagi H, Nagano H, Sakaida I, Takami T, Yamasaki T.
    • Journal Title

      Ann Clin Biochem.

      Volume: 59(6) Issue: 6 Pages: 396-403

    • DOI

      10.1177/00045632221115559

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose2021

    • Author(s)
      Fujisawa K, Takami T, Okubo S, Nishimura Y, Yamada Y, Kondo K, Matsumoto T, Yamamoto N, Sakaida I.
    • Journal Title

      Int J Mol Sci.

      Volume: 22(18) Issue: 18 Pages: 9931-9941

    • DOI

      10.3390/ijms22189931

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Seasonal variations in photoperiod affect hepatic metabolism of medaka ( Oryzias latipes )2021

    • Author(s)
      Fujisawa Koichi、Takami Taro、Shintani Haruko、Sasai Nanami、Matsumoto Toshihiko、Yamamoto Naoki、Sakaida Isao
    • Journal Title

      FEBS Open Bio

      Volume: 11 Issue: 4 Pages: 1029-1040

    • DOI

      10.1002/2211-5463.13095

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【肝不全・肝硬変に対する再生療法-最先端の今】開発中の肝再生医療 自己完結型肝硬変再生療法の開発 培養自己骨髄間葉系幹細胞肝動脈投与療法2021

    • Author(s)
      高見 太郎, 松本 俊彦, 坂井田 功
    • Journal Title

      臨床消化器内科

      Volume: 36(13) Pages: 1660-1666

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Metabolic Alterations in Spheroid-Cultured Hepatic Stellate Cells.2020

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

      Int J Mol Sci.

      Volume: 21(10) Issue: 10 Pages: 3451-3455

    • DOI

      10.3390/ijms21103451

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dantrolene prevents hepatic steatosis by reducing cytoplasmic Ca 2+ level and ER stress2020

    • Author(s)
      Tamitani M, Yamamoto T, Yamamoto N, Fujisawa K, Tanaka S, Nakamura Y, Uchinoumi H, Oda T, Okuda S, Takami T, Kobayashi S, Sakaida I, Yano M.
    • Journal Title

      Biochem Biophys Rep.

      Volume: 23:100787. Pages: 100787-100793

    • DOI

      10.1016/j.bbrep.2020.100787

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesenchymal Stem Cells Induce a Fibrolytic Phenotype By Regulating mmu-miR-6769b-5p Expression in Macrophages.2020

    • Author(s)
      Nishi M, Matsumoto T, Fujisawa K, Suehiro Y, Takami T, Yamamoto N, Yamasaki T, Sakaida I.
    • Journal Title

      Stem Cells Dev.

      Volume: 29(22) Issue: 22 Pages: 1457-1466

    • DOI

      10.1089/scd.2020.0123

    • 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] 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 T, Takami T, Fujisawa K, Matsumoto T, Yamamoto N, Sakaida I.
    • Journal Title

      J Clin Biochem Nutr.

      Volume: 66(3) Pages: 213-223

    • NAID

      130007839286

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 医師主導治験「自己完結型肝硬変再生療法」の開発とNASH肝硬変への有効性評価2022

    • Author(s)
      高見太郎, 松本俊彦, 大田久美江, 児玉雅季, 藤村瑠意, 小島奈緒美, 山本直樹, 坂井田功
    • Organizer
      第21回 日本再生医療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 培養自己骨髄間葉系幹細胞投与療法に対するexosomeを用いた補助療法の開発2022

    • Author(s)
      原和冴, 松本俊彦, 藤澤浩一, 山本直樹, 高見太郎
    • Organizer
      第21回 日本再生医療学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 肝線維化研究Revisited-肝臓学のBiologyからTranslationalへ 肝星細胞とマクロファージの細胞間相互作用におけるmiR-142-3pの役割2022

    • Author(s)
      松本 俊彦, 山本 直樹, 高見 太郎
    • Organizer
      第58回日本肝臓学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 高齢者肝硬変治療の現状と再生医療の期待2022

    • Author(s)
      高見 太郎
    • Organizer
      第24回日本高齢消化器病学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 培養自己骨髄間葉系幹細胞肝動脈投与による医師主導治験「自己完結型肝硬変再生療法」の開始2021

    • Author(s)
      高見太郎, 松本俊彦, 藤澤浩一, 大田久美恵, 藤村瑠意, 小島奈緒美, 丸本芳雄, 石川剛, 山崎隆弘, 坂井田功
    • Organizer
      第20回 日本再生医療学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 鉄キレート剤(DFO)投与により起こる代謝変化を標的にした抗癌剤併用療法の検討2021

    • Author(s)
      藤澤浩一, 松本俊彦, 山本直樹, 高見太郎
    • Organizer
      第28回 肝細胞研究会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 肝病態形成における肝非実質細胞の役割と治療標的 肝非実質細胞の細胞間相互作用に関連する抗線維化核酸治療薬の開発に向けた検討2021

    • Author(s)
      松本 俊彦, 山崎 隆弘, 高見 太郎
    • Organizer
      第25回日本肝臓学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 消化器領域における再生医療の研究と新たな臨床応用 肝硬変に対する医師主導治験「自己完結型肝硬変再生療法」の開発とNASH肝硬変モデルに対する有効性評価2021

    • Author(s)
      高見 太郎, 松本 俊彦, 坂井田 功
    • Organizer
      第25回日本肝臓学会大会
    • Related Report
      2021 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2020

    • Author(s)
      高見太郎, 松本俊彦, 原和冴, 佐々木嶺, 宮地隆史, 大田久美恵, 藤澤浩一, 藤村瑠意, 小島奈緒美, 坂井田功
    • Organizer
      第19回 日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 健常異種動物の骨髄上清による培養骨髄間葉系幹細胞の高品質化2020

    • Author(s)
      宮地隆史, 高見太郎,藤澤浩一, 松本俊彦, 坂井田功
    • Organizer
      第19回 日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Hsa-miR-5682は肝星細胞における細胞外マトリックス蛋白および分子シャペロンの発現を網羅的に抑制する2020

    • Author(s)
      松本俊彦, 藤澤浩一, 高見太郎, 山本直樹, 末広寛, 山崎隆弘, 坂井田功
    • Organizer
      第106回日本消化器病学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 骨髄由来間葉系幹細胞におけるストレス応答機構の解明2020

    • Author(s)
      笹井奈々実, 藤澤浩一, 高見太郎, 松本俊彦, 山本直樹, 西川潤, 坂井田功
    • Organizer
      第19回 日本再生医療学会総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 健常異種動物の骨髄上清による培養骨髄間葉系幹細胞の高品質化2020

    • Author(s)
      高見太郎, 宮地隆史, 藤澤浩一, 松本俊彦, 山本直樹,坂井田功
    • Organizer
      第27回肝細胞研究会総会
    • Related Report
      2020 Annual Research Report
  • [Remarks] 山口大学大学院医学系研究科 消化器内科

    • URL

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

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report 2020 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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