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Establishment of neovascularization-inducing technology accompanied with hematopoiesis by utilizing Periodontal ligament derived stem cells

Research Project

Project/Area Number 24792149
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Dental engineering/Regenerative dentistry
Research InstitutionHokkaido University

Principal Investigator

OKUBO Naoto  北海道大学, 薬学研究科(研究院), 研究員 (00553207)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords再生医療 / 造血幹細胞 / 血管新生 / 歯根膜幹細胞 / 三次元培養
Outline of Final Research Achievements

We reported to establish the periodontal ligament (PDL) derived stem cells, which had the capacity to construct blood vessel structures. Thereafter, we observed these PDL cells expressed multiple hematopoietic stem cell markers and possessed the capacity to induce eosinophilic blood cells inside the constructed vessel lumen in our three-dimensional culture. To identify the vital genes associated with regulation of hemangioblastic capacity, we performed cDNA microarray analysis and then selected one transcription factor.
Subsequently, we constructed adenoviral vector including the sequence of selected gene and transfected the vector with the PDL cells. According to this treatment, both angiogenic and hematopoietic capacity were significantly enhanced. Futhermore, the gene expression of hematopoietic marker gene; c-kit(CD117) was upregulated in viral titer-dependent manner. In consequence of these data, we identified one vital gene to regulate hemangioblastic capacity of the PDL cells.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (28 results)

All 2015 2014 2013 2012 2011 Other

All Journal Article (12 results) (of which Peer Reviewed: 10 results,  Open Access: 4 results,  Acknowledgement Compliant: 2 results) Presentation (13 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats.2015

    • Author(s)
      Onishi R, Ohnishi S, Higashi R, Watari M, Yamahara K, Okubo N, Nakagawa K, Katsurada K, Suda G, Natsuizaka M, Takeda H, Sakamoto N
    • Journal Title

      Cell Transplantation

      Volume: -

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Serotonin 2C receptor contributes to gender differences in stress-induced hypophagia in aged mice.2015

    • Author(s)
      Yamada C, Sadakane C, Nahata C, Saegusa Y, Nakagawa K, Okubo N, Ohnishi S, Hattori T, Takeda H
    • Journal Title

      Psychoneuroendocrinology

      Volume: 55 Pages: 81-93

    • DOI

      10.1016/j.psyneuen.2015.02.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells.2014

    • Author(s)
      Aomatsu, E., Takahashi, N., Sawada, S., Okubo, N., Hasegawa, T., Taira, M., Miura, H., Ishisaki, A., and Chosa, N.
    • Journal Title

      Sci. Rep.

      Volume: 4 Issue: 1 Pages: 3652-3652

    • DOI

      10.1038/srep03652

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PDGF-induced PI3K-mediated signal enhances TGF-βinduced osteogenic differentiation of human mesenchymal stem cells in the TGF-β-activated MEK-dependent manner2014

    • Author(s)
      Jun Yokota, Naoyuki Chosa, Shunsuke Sawada, Naoto Okubo, Noriko Takahashi, Tomokazu Hasegawa, Hisatomo Kondo, Akira Ishisaki
    • Journal Title

      International Journal of Molecular Medicine

      Volume: 33 Issue: 3 Pages: 534-542

    • DOI

      10.3892/ijmm.2013.1606

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] EGF positively regulates the proliferation and migration, and negatively regulates the myofibroblast differentiation of periodontal ligament-derived endothelial progenitor cells through MEK/ERK- and JNK-dependent signals.2013

    • Author(s)
      Kimura, H., Okubo, N., Chosa, N., Kyakumoto, S., Kamo, M., Miura, H. and Ishisaki, A
    • Journal Title

      Cell. Physiol. Biochem.

      Volume: 32 Issue: 4 Pages: 899-914

    • DOI

      10.1159/000354493

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pathophysiologic Basis of Anorexia: Focus on the Interaction between Ghrelin Dynamics and the Serotonergic System2013

    • Author(s)
      Takeda H, Nakagawa K, Okubo N, Nishimura M, Muto S, Ohnishi S, Sakamoto N, Hosono H, Asaka M.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 36(9) Pages: 1401-1405

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transforming growth factor-β1 induces epithelialmesenchymal transition and integrin α3β1-mediated cell migration of HSC-4 human squamous cell carcinoma cells through Slug2013

    • Author(s)
      Saito D, Kyakumoto S, Chosa N, Ibi M, Takahashi,N, Okubo N, Sawada S, Ishisaki A, & Kamo M
    • Journal Title

      J. Biochem

      Volume: 153 Issue: 3 Pages: 303-315

    • DOI

      10.1093/jb/mvs144

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 六君子湯による摂食不振・悪液質の改善2013

    • Author(s)
      武田 宏司, 中川 浩治, 西村 三恵, 大久保 直登, 細野 秀崇, 浅香 正博, 武藤 修一, 大西 俊介, 坂 本 直哉
    • Journal Title

      Jounal of Gastrointestinal Reserch

      Volume: 21(1) Pages: 48-58

    • Related Report
      2013 Research-status Report
  • [Journal Article] 六君子湯による摂食不振・悪液質の改善2013

    • Author(s)
      武田 宏司, 中川 浩治, 西村 三恵, 大久保 直登, 細野 秀崇, 浅香 正博, 武藤 修一, 大西 俊介, 坂本 直哉
    • Journal Title

      Jounal of Gastrointestinal Reserch  2013;Vol21 no.1

      Volume: Vol21 no.1 Pages: 48-58

    • Related Report
      2012 Research-status Report
  • [Journal Article] TGF-β-operated growth inhibition and translineage commitment into smooth muscle cells of periodontal ligamentderived endothelial progenitor cells through Smad- and p38 MAPK dependentsignals2012

    • Author(s)
      Yoshida M, Okubo N, Chosa N, Hasegawa T, Ibi M, Kamo M, Kyakumoto S, & Ishisaki A
    • Journal Title

      Int. J. Biol. Sci.

      Volume: 8 Issue: 7 Pages: 1062-1074

    • DOI

      10.7150/ijbs.4488

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fibroblast growth factor-1-induced ERK1/2 signaling reciprocally regulates proliferation and smooth muscle cell differentiation of ligament-derived endothelial progenitor cell-like cells2012

    • Author(s)
      Takahahi M, Okubo N, Chosa N, Takahashi N, Miho I, Kamo M, Mizuki H, Ishisaki A, & Kyakumoto S
    • Journal Title

      Int. J. Mol.Med.

      Volume: 29 Pages: 357-364

    • DOI

      10.3892/ijmm.2011.847

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dental pulp cells derived from permanent teeth express higher levels of R-cadher in than do deciduous teeth : Implications of the correlation between R-cadherin expression and restriction of multipotency in mesenchymal stem cells2011

    • Author(s)
      Takahashi N
    • Journal Title

      Archives of Oral Biology

      Volume: 57 Issue: 1 Pages: 44-51

    • DOI

      10.1016/j.archoralbio.2011.07.013

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] Establishment of a co-culture system for simultaneous proliferation of td-Tomato-expressing mouse bone marrow-derived mesenchymal stem cells and undifferentiated blood cells.2014

    • Author(s)
      Naoki Takizawa, Seiko Kyakumoto, Naoto Okubo, Naoyuki Chosa, Miho Ibi, Hideaki Fujiwara, Masaharu Kamo1, Masato Otuka, Takashi Yaegashi , Akira Ishisaki.
    • Organizer
      第37回日本分子生物学会・総会
    • Place of Presentation
      福岡県 福岡国際会議場
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] EGFによるPDL由来EPCの増殖、分化制御2013

    • Author(s)
      木村仁迪 大久保直登 帖佐直幸 衣斐美歩 客本斉子 加茂政晴 金野吉晃 三浦廣行  石崎明
    • Organizer
      第55回歯科基礎医学会学術大会・総会
    • Place of Presentation
      岡山・岡山コンベンションセンター
    • Related Report
      2013 Research-status Report
  • [Presentation] サイトカイン様ペプチドSCRG1は間葉系幹細胞の骨ならびに脂肪分化を抑制する2013

    • Author(s)
      青松恵美子 帖佐直幸 大久保直登 衣斐美歩 高橋典子 客本斉子 加茂政晴 長谷川智一 佐藤和朗 三浦廣行 石崎明
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] EGFが歯周靭帯由来血管内皮前駆細胞の増殖と筋線維芽細胞分化に与える影響について2013

    • Author(s)
      木村仁迪 大久保直登 帖佐直幸 衣斐美歩 客本斉子 加茂政晴 金野吉晃 三浦廣行  石崎明
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜・パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] TGF-βを介したヒト口腔扁平上皮癌細胞HSC-4における上皮間葉転換について2012

    • Author(s)
      斎藤大嗣 帖佐直幸 客本斉子 高橋典子 大久保直登 衣斐美歩 水城春美 石崎明 加茂政晴
    • Organizer
      日本分子生物学会第12回春季シンポジウム
    • Place of Presentation
      石和温泉 慶山 (山梨県)
    • Related Report
      2012 Research-status Report
  • [Presentation] TGF-βによる歯周靭帯由来血管内皮前駆細胞様細胞の増殖抑制と平滑筋細胞様分化のシグナル解析2012

    • Author(s)
      客本斉子 吉田茉莉子 大久保直登 帖佐直幸 長谷川智一 高橋典子 衣斐美歩 加茂政晴  石崎明
    • Organizer
      第54回歯科基礎医学会学術大会・総会
    • Place of Presentation
      奥羽大学 (福島県郡山市富田町)
    • Related Report
      2012 Research-status Report
  • [Presentation] TGF-βにより誘導された上皮間葉転換に伴うヒト口腔扁平上皮癌細胞の細胞運動の解析2012

    • Author(s)
      齋藤大嗣 帖佐直幸 客本斉子 高橋典子 大久保直登 衣斐美歩 石崎明 加茂政晴
    • Organizer
      第54回歯科基礎医学会学術大会・総会
    • Place of Presentation
      奥羽大学 (福島県郡山市富田町)
    • Related Report
      2012 Research-status Report
  • [Presentation] EGFが歯周靭帯由来血管内皮前駆細胞様細胞の増殖と筋線維芽細胞分化に与える影響について2012

    • Author(s)
      木村仁迪 大久保直登 帖佐直幸 衣斐美歩 客本斉子 加茂政晴 金野吉晃 三浦廣行 石崎明
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡 (福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] TGF-βとIGF-1、PDGFまたはVEGFの同時刺激は間葉系幹細胞の骨分化を促進する2012

    • Author(s)
      横田潤 帖佐直幸 大久保直登 衣斐美歩 高橋典子 客本斉子 加茂政晴 近藤尚知 石崎明
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡 (福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 間葉系幹細胞由来サイトカイン様ペプチドSCRG1は破骨細胞分化を抑制する2012

    • Author(s)
      青松恵美子 帖佐直幸 大久保直登 衣斐美歩 高橋典子 客本斉子 加茂政晴 佐藤和朗 三浦廣行 石崎明
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡 (福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] 歯根膜由来内皮前駆細胞様線維芽細胞におけるTGF-β誘導性増殖抑制、平滑筋初期分化へのSmad ならびにp38 MAPK経路の関与2012

    • Author(s)
      吉田茉莉子 大久保直登 帖佐直幸 長谷川智一 衣斐美歩 客本斉子 加茂政晴 石崎明
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡 (福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト口腔扁平上皮癌細胞におけるTGF-β1による上皮間葉転換に伴う細胞遊走能の解析2012

    • Author(s)
      齋藤大嗣 帖佐直幸 客本斉子 高橋典子 大久保直登 衣斐美歩 水城春美 石崎明  加茂政晴
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡 (福岡県)
    • Related Report
      2012 Research-status Report
  • [Presentation] ファイブロサイトに注目した口腔領域疾患発症機構の解明2012

    • Author(s)
      衣斐美歩 大久保直登 堀江沙和 帖佐直幸 吉田茉莉子 加茂政晴 客本斉子 大塚正人   佐原資謹 藤村朗 石崎明
    • Organizer
      第35回日本分子生物学会年会
    • Place of Presentation
      福岡国際会議場・マリンメッセ福岡 (福岡県)
    • Related Report
      2012 Research-status Report
  • [Book] Tooth Materials Science and Clinical Applications (one chapter 担当)2015

    • Author(s)
      Masaru Murata, In-Woong Um, (Naoto Okubo, Akira Ishisaki)
    • Publisher
      Quintessence Publisher
    • Related Report
      2013 Research-status Report
  • [Book] Advances in Oral Tissue Engineering2014

    • Author(s)
      Masaru Murata, In-Woong Um, (Naoto Okubo, Akira Ishisaki)
    • Total Pages
      72
    • Publisher
      Quintessence Publishing
    • Related Report
      2014 Annual Research Report
  • [Remarks] 北海道大学大学院薬学研究院臨床病態解析学

    • URL

      http://www.pharm.hokudai.ac.jp/byoutai/index.html

    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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