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The analysis and identification of bome marrow drived liver repair cell

Research Project

Project/Area Number 15K09005
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Gastroenterology
Research InstitutionYamaguchi University

Principal Investigator

YAMAMOTO Naoki  山口大学, 大学教育機構, 准教授 (90448283)

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)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords再生医療 / 電子顕微鏡 / 骨髄細胞 / 幹細胞 / 免疫電顕 / 肝線維化 / GFP/CCl4モデル / MMP9 / 肝硬変 / 培養骨髄細胞 / EpCAM / 骨髄幹細胞 / 肝臓再生 / 肝線維化抑制
Outline of Final Research Achievements

We analyzed the characterization of the infused GFP-postive BMC using both EM and Immuno EM(IEM).We analyzed the image of IEM, comparing with the character of positive cells by immunohistochemistry and fluorescence staining(Antibody:GFP,MMP9, hepatoblastmarker-Liv2,CD44,A6,EpCAM,CXCR4,transcription regulator-maternal of inhibitor of differentiation-Maid).
We had two kinds of GFP positive BMCs.One group of GFP positive BMCs(MMP9 positive cells,CXCR4 positive cells)were similar to hepatocyte in size and located around fiber.These cells were round forms and had the increase of lysosome structure in cytoplasm and located on fiber in hepatic cord and repaired fibrosis. The other group cells(A6 positive cells, Liv2 positive cells, EpCAM positive cells) were small size and located in destructive area.These cells had high N/C ratio and smaller than hepatocyte and migrated into damaged cell area and had the phagocytic capacity. We detected that CXCR4 positive BMCs repaird liver fibrosis.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (39 results)

All 2017 2016 2015 2014 Other

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 14 results,  Acknowledgement Compliant: 5 results) Presentation (22 results) (of which Int'l Joint Research: 9 results) Remarks (3 results)

  • [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
  • [Journal Article] Evaluating effects of L-carnitine on human bone-marrow-derived mesenchymal stem cells.2017

    • Author(s)
      Fujisawa K, Takami T (Corresponding), Fukui Y, Quintanilha LF, Matsumoto T, Yamamoto N, Sakaida I.
    • Journal Title

      Cell Tissue Res

      Volume: 368(2) Issue: 2 Pages: 301-310

    • DOI

      10.1007/s00441-017-2569-0

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effectiveness of tolvaptan monotherapy and low-dose furosemide/tolvaptan combination therapy for hepatoprotection and diuresis in a rat cirrhotic model2017

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

      Journal of Clinical Biochemistry and Nutrition

      Volume: 61 Issue: 1 Pages: 53-59

    • DOI

      10.3164/jcbn.16-122

    • NAID

      130006847656

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of the effects of L-carnitine on medaka (Oryzias latipes) fatty liver.2017

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

      Sci Rep.

      Volume: 7(1) Issue: 1 Pages: 2749-2749

    • DOI

      10.1038/s41598-017-02924-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of an oral iron chelator, deferasirox, on advanced hepatocellular carcinoma.2016

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

      World J Gastroenterol.

      Volume: 22(40) Pages: 8967-8977

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Deferasirox, a novel oral iron chelator, shows antiproliferative activity against pancreatic cancer in vitro and in vivo.2016

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

      BMC Cancer.

      Volume: 16 Issue: 1 Pages: 702-702

    • DOI

      10.1186/s12885-016-2744-9

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib2016

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

      Journal of Clinical Biochemistry and Nutrition

      Volume: 58 Issue: 3 Pages: 202-209

    • DOI

      10.3164/jcbn.15-127

    • NAID

      130005149374

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4.2016

    • Author(s)
      Fujisawa K, Terai S, Takami T, Yamamoto N, Yamasaki T, Matsumoto T, Yamaguchi K, Owada Y, Nishina H, Noma T, Sakaida I.
    • Journal Title

      J Exp Clin Cancer Res.

      Volume: - Issue: 1 Pages: 48-48

    • DOI

      10.1186/s13046-016-0322-2

    • NAID

      120006937642

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib2016

    • Author(s)
      Yamamoto N, Yamasaki T,Takami T,Matsumoto T,Fujisawa K,Saeki I,Uchida K, Terai S, Sakaida I,
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: in press

    • NAID

      130005149374

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Circadian variations in the liver metabolites of medaka (Oryzias latipes).2015

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

      Sci Rep.

      Volume: - Issue: 1 Pages: 20916-20916

    • DOI

      10.1038/srep20916

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evidence for a Role of the Transcriptional Regulator Maid in Tumorigenesis and Aging.2015

    • Author(s)
      Fujisawa K, Terai S, Matsumoto T, Takami T, Yamamoto N, Nishina H, Furutani-Seiki M, Sakaida I.
    • Journal Title

      PLoS One

      Volume: 10(6) Issue: 6 Pages: e0129950-e0129950

    • DOI

      10.1371/journal.pone.0129950

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] A new therapeutic assessment score for advanced hepatocellular carcinoma patients receiving hepatic arterial infusion chemotherapy.2015

    • Author(s)
      Saeki I, Yamasaki T, Tanabe N, Iwamoto T, Matsumoto T, Urata Y, Hidaka I, Ishikawa T, Takami T, Yamamoto N, Uchida K, Terai S, Sakaida I.
    • Journal Title

      PLoS One.

      Volume: 10(5) Issue: 5 Pages: e0126649-e0126649

    • DOI

      10.1371/journal.pone.0126649

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Enhanced survival of mice infused with bone marrow-derived as compared with adipose-derived mesenchymal stem cells.2014

    • Author(s)
      Shiratsuki S, Terai S, Murata Y, Takami T, Yamamoto N, Fujisawa K, Burganova G, Quintanilha LF, Sakaida I.
    • Journal Title

      Hepatol Res

      Volume: - Issue: 13 Pages: 1353-1359

    • DOI

      10.1111/hepr.12507

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 肝硬変症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 藤澤 浩一 山本 直樹 坂井田 功
    • Organizer
      第16回日本再生医療学会総会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2017-03-07
    • Related Report
      2016 Research-status Report
  • [Presentation] Infused bone marrow derived cells have two capacities that repair of fibrosis and phagocytosis of damaged cells2017

    • Author(s)
      Naoki Yamamoto,Taro Takami, Shuji Terai, Koichi Uchida, Koichi Fujisawa, Toshihiko Matsumoto, Hiroshi Nishina,Isao Sakaida.
    • Organizer
      The 14th Annual Meeting of the International Society for Stem Cell Research(ISSCR) Boston
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nonclinical proof-of-concept for "hepatic artery infusion of cultured autologous bone marrow mesenchymal stem cells" in a canine liver fibrosis model2017

    • Author(s)
      Tatsuro Nishimura, Taro Takami, Ryo Sasaki, Yuki Aibe, Takashi Matsuda, Toshihiko, Matsumoto, Koichi Fujisawa, Naoki Yamamoto, Isao Sakaida
    • Organizer
      The Liver Meeting 2017, AASLD Washington DC
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マクロファージRho family GTPaseを標的とした肝線維溶解療法に向けた基盤研究2017

    • Author(s)
      松本 俊彦、仁志 麻衣子、藤澤 浩一、高見 太郎、山本 直樹、坂井田 功
    • Organizer
      第53回日本肝臓学会総会 広島
    • Related Report
      2017 Annual Research Report
  • [Presentation] BCAA製剤によるSorafenibの治療効果増強と副作用軽減作用の解析2017

    • Author(s)
      山本 直樹、高見 太郎、藤澤 浩一、松本 俊彦、内田 耕一、坂井田 功
    • Organizer
      第53回日本肝臓学会総会 広島
    • Related Report
      2017 Annual Research Report
  • [Presentation] 骨髄間葉系幹細胞によるマクロファージMMP発現の制御2017

    • Author(s)
      仁志 麻衣子、松本 俊彦、藤澤 浩一、高見 太郎、山本 直樹、坂井田 功
    • Organizer
      第53回日本肝臓学会総会 広島
    • Related Report
      2017 Annual Research Report
  • [Presentation] イヌ線維化評価モデルによる培養自己骨髄間葉系幹細胞肝動脈投与の非臨床Proof of Conceptの取得2017

    • Author(s)
      西村 達朗、高見 太郎、佐々木 嶺、相部 祐希、松田 崇史、山本 直樹、坂井田 功
    • Organizer
      第53回日本肝臓学会総会 広島
    • Related Report
      2017 Annual Research Report
  • [Presentation] Rho family GTPases regulate MMPs expression and pro-inflammatory phenotype of macrophages in fibrotic liver.2016

    • Author(s)
      Toshihiko Matsumoto, Maiko Nishi, Koichi Fujisawa, Taro Takami, Naoki Yamamoto, Isao Sakaida
    • Organizer
      The Liver Meeting 2016, AASLD
    • Place of Presentation
      Boston USA
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cultured bone marrow-derived mesenchymal stem cells contributed to improving liver cirrhosis through both the direct stabilization of redox homeostasis and cell-cell interaction with macrophages2016

    • Author(s)
      Taro Takami, Toshihiko Matsumoto, Maiko Nishi, Koichi Fujisawa, Naoki Yamamoto, Isao Sakaida
    • Organizer
      The Liver Meeting 2016, AASLD
    • Place of Presentation
      Boston USA
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The efficacy and safety of liver regeneration therapy by hepatic arterial infusion of cultured autologous bone marrow mesenchymal stem cells in our established canine cirrhotic model2016

    • Author(s)
      Yuki Aibe, Taro Takami, Ryo Sasaki, Tatsuro Nishimura, Takashi Matsuda, Toshihiko Matsumoto, Koichi Fujisawa, Tsuyoshi Ishikawa, Naoki Yamamoto, Kenji Tani, Yasuho Taura, Isao Sakaida
    • Organizer
      The Liver Meeting 2016, AASLD
    • Place of Presentation
      Boston USA
    • Year and Date
      2016-11-11
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 肝硬変症に対する自己骨髄細胞を用いた肝臓再生療法2016

    • Author(s)
      高見 太郎 松本 俊彦 山本 直樹 藤澤 浩一 坂井田 功
    • Organizer
      JDDW 2016
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2016-11-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Infused bone marrow derived cells have two capacities that repair of fibrosis and phagocytosis of damaged cells2016

    • Author(s)
      Naoki Yamamoto,Taro Takami, Toshihiko Matsumoto, Koichi Uchida, Koichi Fujisawa, Isao Sakaida
    • Organizer
      International Society for Stem Cell Research 2016 (ISSCR2016)
    • Place of Presentation
      San Francisco USA
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Arterial infusion of cultured autologous bone marrow mesenchymal stem cells has a stronger therapeutic effect on liver cirrhosis in our established canine model2016

    • Author(s)
      Taro Takami, Yuki Aibe, Tatsuro Nishimura, Takashi Matsuda, Toshihiko Matsumoto, Koichi Fujisawa, Naoki Yamamoto, Kenji Tani, Yasuho Taura, Isao Sakaida
    • Organizer
      International Society for Stem Cell Research 2016 (ISSCR2016)
    • Place of Presentation
      San Francisco USA
    • Year and Date
      2016-06-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] イヌ肝線維化モデル系における培養自己骨髄間葉系幹細胞投与の有効性評価2016

    • Author(s)
      相部 祐希、高見 太郎、西村 達朗、佐々木 嶺、松田 崇史、藤澤 浩一、松本俊彦、石川 剛、山本 直樹、坂井田 功
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ幕張
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 進行肝細胞癌に対する経口鉄キレート剤の治療戦略2016

    • Author(s)
      佐伯 一成、山本 直樹、高見太郎、山﨑隆弘、坂井田 功
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ幕張(千葉県・千葉市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 肝硬変症に対する新規SGLT2(Sodium-Glucose Co-Transporter2)阻害剤の治療効果の基礎的検証と機序解明2016

    • Author(s)
      山本 直樹、高見 太郎、藤澤 浩一、松本俊彦、坂井田 功
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ幕張(千葉県・千葉市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] レボカルニチンによるSASP現象抑制効果によるNAFLD治療の可能性2016

    • Author(s)
      山本 直樹、高見 太郎、藤澤 浩一、松本俊彦、坂井田 功
    • Organizer
      第52回日本肝臓学会総会
    • Place of Presentation
      ホテルニューオータニ幕張(千葉県・千葉市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Presentation] 肝臓再生療法における骨髄由来肝臓修復細胞の特徴2016

    • Author(s)
      山本 直樹
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場 (大阪府・大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Research-status Report
  • [Presentation] L-carnitine prevents liver fibrosis and preneoplastic lesions in rat liver cirrhosis model induced by a choline-deficient L-amino acid-defined diet(CDAA) and Diethylnitrosamine (DEN)2015

    • Author(s)
      Naoki Yamamoto
    • Organizer
      The 23th United European Gastroenterology Week (UEGW 2015)
    • Place of Presentation
      Barcelona Convention Center (Spain)
    • Year and Date
      2015-10-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Infused bone marrow derived cells have two capacities that phagocytosis of damaged cells and repair of fibrosis in mice2015

    • Author(s)
      Naoki Yamamoto
    • Organizer
      The 12th Annual Meeting of the International Society for Stem Cell Research (ISSCR) 2015
    • Place of Presentation
      Stockholm convention center (Sweden)
    • Year and Date
      2015-06-24
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 新規SGLT2(Sodium-Glucose Co-Transporter2)阻害剤の肝線維化抑制効果の基礎的検討2015

    • Author(s)
      山本 直樹
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本ホテル日航(熊本県・熊本市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Presentation] レボカルニチンによるNAFLD治療効果の基礎的検討2015

    • Author(s)
      山本 直樹
    • Organizer
      第51回日本肝臓学会総会
    • Place of Presentation
      熊本ホテル日航(熊本県・熊本市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Research-status Report
  • [Remarks]

    • URL

      http://www.ichinai-yamaguchi.jp/contents1/detail.php?id=58

    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2016 Research-status Report
  • [Remarks] http://www.ichinai-yamaguchi.jp/

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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