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Development of novel high quality mesenchymal stem cells for regenerative medicine

Research Project

Project/Area Number 18K15815
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionYamaguchi University

Principal Investigator

Fujisawa Koichi  山口大学, 医学部, 講師(寄附講座等) (00448284)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords再生医療 / 肝幹細胞 / 間葉系幹細胞 / 再生 / 肝臓 / MSC / 線維化 / 幹細胞
Outline of Final Research Achievements

Mesenchymal stem cells (MSC) are used in regenerative medicine applications. We conducted a comparative assessment of metabolic changes in MSCs induced by deferoxamine (DFO), an iron chelator that can be used as a mimetic hypoxia reagent useful for maintaining cells in the same metabolic state even in low-oxygen environments, and MSCs that underwent low-oxygen treatment.
Although inhibition of cell division was observed after administering DFO at a relatively low concentration, both decreased mitochondrial activity and an inhibitory effect on apoptosis were also observed, suggesting the possibility that DFO at low concentrations may be useful for MSC preconditioning. In this study, we comprehensively evaluated the effect of DFO on various metabolites in cultured human mesenchymal stem cells (BMSC) as well as the feasibility possibility of replacing the hypoxic culturing technique by treating BMSCs with DFO.

Academic Significance and Societal Importance of the Research Achievements

鉄キレート剤 (DFO) 投与により細胞増殖抑制は現れるものの、アポトーシス抑制効果を示し、低酸素誘導性タンパクの発現上昇と、ミトコンドリア機能低下を起こすDFO の濃度での培養を行うことが有用であることを解明した。また代謝解析により、低酸素培養の代替えにDFO投与が有用であることがわかった。本研究のデータは今後MSCを用いた再生医療を行う際に必要なMSCの調製に重要な知見になることが示された。

Report

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

    (17 results)

All 2021 2020 2019 2018

All Journal Article (12 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (5 results)

  • [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
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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 2019 Research-status 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 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 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] NUPR1 acts as a pro-survival factor in human bone marrow-derived mesenchymal stem cells and is induced by the hypoxia mimetic reagent deferoxamine2019

    • Author(s)
      Matsunaga Kazuhito、Fujisawa Koichi、Takami Taro、Burganova Guzel、Sasai Nanami、Matsumoto Toshihiko、Yamamoto Naoki、Sakaida Isao
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 64 Issue: 3 Pages: 209-216

    • DOI

      10.3164/jcbn.18-112

    • NAID

      130007641429

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2019 Research-status Report 2018 Research-status 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
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Issue: 8 Pages: 1226-1236

    • DOI

      10.1002/stem.2826

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mitochondrial Activity and Unfolded Protein Response are Required for Neutrophil Differentiation.2018

    • Author(s)
      Tanimura A, Miyoshi K, Horiguchi T, Hagita H, Fujisawa K, Noma T
    • Journal Title

      Cell Physiol Biochem

      Volume: 47 Issue: 5 Pages: 1936-1950

    • DOI

      10.1159/000491464

    • NAID

      120006550810

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 2020/5/18
    • Related Report
      2020 Annual Research Report
  • [Presentation] オートファジーに関わる NUPR1に着目した骨髄由来間葉系幹細胞のストレス耐性機構の評価2020

    • Author(s)
      笹井 奈々実、藤澤 浩一、松本 俊彦、高見 太郎、山本 直樹、西川 潤、坂井田 功
    • Organizer
      第27回肝細胞研究会 2020/12/15,16
    • Related Report
      2020 Annual Research Report
  • [Presentation] メダカモデルを用いた肝脂肪化の評価2019

    • Author(s)
      藤澤浩一、高見太郎、坂井田功
    • Organizer
      プロメテウスの会
    • Related Report
      2018 Research-status Report
  • [Presentation] メダカ脂肪肝の非侵襲的モデルについて2018

    • Author(s)
      藤澤浩一, 高見太郎, 福井悠美, 松本俊彦, 山本直樹, 坂井田功
    • Organizer
      小型魚類研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脂肪食投与によるメダカ脂肪肝の代謝変化とTransparent(透明)メダカを用いたUltrasoundによる非侵襲的脂肪肝評価2018

    • Author(s)
      藤澤浩一, 高見太郎, 福井悠美, 松本俊彦, 山本直樹, 坂井田功
    • Organizer
      日本肝臓学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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