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Three-dimensional multilayers of smooth muscle cells as a new experimental model for vascular biology

Research Project

Project/Area Number 24659100
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field General physiology
Research InstitutionYokohama City University

Principal Investigator

YOKOYAMA Utako  横浜市立大学, 医学部, 講師 (70404994)

Co-Investigator(Renkei-kenkyūsha) ISHIKAWA Yoshihiro  横山市立大学, 医学研究科, 教授 (40305470)
ICHIKAWA Yasuhiro  横山市立大学, 医学部, 助教 (10555121)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords循環器・高血圧 / 生理学 / ナノバイオ / 細胞・組織 / 三次元培養 / 弾性線維 / 動脈硬化
Research Abstract

Elastic fiber formation is disrupted with age and by health conditions including aneurysms and atherosclerosis. Despite considerable progress in the understanding of elastogenesis using the planar culture system and genetically modified animals, it remains difficult to restore elastic fibers in diseased vessels. To further study the molecular mechanisms, we created in vitro three-dimensional vascular constructs. Three-dimensional cellular multilayers (3DCMs), which consisted of seven layers of neonatal rat aortic SMCs cultured in 1% fetal bovine serum in DMEM medium, exhibited layered elastic fibers and differentiated smooth muscle cell phenotype within seven days of being in a static culture condition. Furthermore, infiltration of THP-1-derived macrophages decreased the surrounding elastic fiber formation in 3DCMs. 3DCMs may offer a new experimental vascular model to explore pharmacological therapeutic strategies for abnormal vascular remodeling.

Report

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

    (42 results)

All 2014 2013 2012 Other

All Journal Article (18 results) (of which Peer Reviewed: 14 results,  Open Access: 3 results) Presentation (16 results) (of which Invited: 11 results) Book (3 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Three-Dimensional Multilayers of Smooth Muscle Cells as a New Experimental Model for Vascular Elastic Fiber Formation Studies.2014

    • Author(s)
      Ishiwata R, Yokoyama U, Matsusaki M, Yoshiya A, Kadowaki K, Ichikaww Y, Umemura M, Fujita T, Minamisawa S, Shimoda H, Mitsuru Akashi M, and Ishikawa Y.
    • Journal Title

      Atherosclerosis.

      Volume: 233 Issue: 2 Pages: 590-600

    • DOI

      10.1016/j.atherosclerosis.2014.01.045

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prostaglandin E2 Inhibits Elastogenesis in the Ductus Arteriosus via EP4 Signaling.2014

    • Author(s)
      Yokoyama U, Minamisawa S, Sh ioda A, Ishiwata R, Jin MH, Masuda M, Asou T, Sugimoto Y, Aoki II, Nakamura T, and Ishikawa Y
    • Journal Title

      Circulation.

      Volume: 129 Issue: 4 Pages: 487-496

    • DOI

      10.1161/circulationaha.113.004726

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The prostanoid EP4 receptor and its signaling pathway.2013

    • Author(s)
      Yokoyama U, Iwatsubo K, Umemura M, Fujita T, and Ishikawa Y.
    • Journal Title

      Pharmacol Rev.

      Volume: 65 Issue: 3 Pages: 1010-1052

    • DOI

      10.1124/pr.112.007195

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 動脈瘤とPGE_22013

    • Author(s)
      横山詩子,金美花,石川義弘
    • Journal Title

      遺伝子医学MOOK

      Volume: 24 Pages: 296-300

    • URL

      http://www.medicaldo.co.p/gene/mook.no24.html

    • Related Report
      2013 Final Research Report
  • [Journal Article] The prostanoid EP4 receptor and its signaling pathway2013

    • Author(s)
      Utako Yokoyama
    • Journal Title

      Pharmacological Reviews

      Volume: 印刷中

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 動脈瘤とPGE22013

    • Author(s)
      横山 詩子
    • Journal Title

      遺伝子医学MOOK

      Volume: 24

    • Related Report
      2012 Research-status Report
  • [Journal Article] Inhibition of EP4 signaling attelluates aortic aneurysm formation2012

    • Author(s)
      Yokoyama U
    • Journal Title

      PLoS One

      Volume: 7 Issue: 5 Pages: e36724-e36724

    • DOI

      10.1371/journal.pone.0036724

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate under both Microgravity and Hypergravity induced by Parabolic Flight2012

    • Author(s)
      Bai Y, Tsunematsu T, Jiao Q, Ohnuki Y, Mototani Y, Shiozawa K, Jin MH, Cai W, Jin HL, Fujita T, Ichikawa Y, Suita K, Kurotani R, Yokoyama U, Sato M, Iwatsubo K, Ishikawa Y, Okumura S
    • Journal Title

      J Pharmacol Sci

      Volume: 119 Pages: 381-9

    • NAID

      10031071685

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/22850613

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Phosphodiesterase Type 3 Dilates the Rat Ductus Arteriosus without Inducing Intimal Thickening2012

    • Author(s)
      I chikawa Y, Yokoyama U, Iwamoto M, Oshikawa J, Okumura S, Sato M, Yokota S, Masuda M, Asou T, Isikawa Y
    • Journal Title

      Circ J

      Volume: 76 Pages: 2456-64

    • NAID

      10030875150

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/22785618

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low-dose Thromboxane A2 Receptor Stimulation Promotes Closure of the Rat Ductus Arteriosus with Minimal Adverse Effects2012

    • Author(s)
      Yokota T, Aida T, Ichikawa Y, Fujita T, Yokoyama U, Minamisawa S
    • Journal Title

      Pediatr Res

      Volume: 72 Issue: 4 Pages: 129-36

    • DOI

      10.1371/journal.pone.0094895

    • Related Report
      2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of ascorbic acid on reactive oxygen species production in chemotherapy and hyperthermia in prostate cancer cells.2012

    • Author(s)
      Fukumura H, et al.
    • Journal Title

      J. Physiol. Sci.

      Volume: 62 Issue: 3 Pages: 251-257

    • DOI

      10.1007/s12576-012-0204-0

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cyclic AMP and Epac in the regulation of tissue fibrosis2012

    • Author(s)
      Insel PA, Murray F, Yokoyama U, Romano S, Yun H, Brown L, Snead A, Lu D, Aroonsakool N
    • Journal Title

      Br. J. Pharmacol

      Volume: 166(2) Issue: 2 Pages: 447-456

    • DOI

      10.1111/j.1476-5381.2012.01847.x

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Morphological and Histological Evaluations of 3D-Layered Blood Vessel Constructs Prepared by Hierarchical Cell Manipulation.2012

    • Author(s)
      Matsusaki M, et al.
    • Journal Title

      J Biomater Sci Polym Ed.

      Volume: 23 Issue: 1-4 Pages: 63-79

    • DOI

      10.1163/092050610x541953

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 三次元血管モデルを用いた動脈硬化性疾患の機序解明Elucidation of Molecular Mechanisms of Atherosclerosis by Three-Dimensional (3D)-Layered Blood Vessel Constructs2012

    • Author(s)
      横山詩子、石渡遼、大島登志男、南沢享、石川義弘
    • Journal Title

      科学と工業

      Volume: 86 Pages: 329-35

    • URL

      http://www.osakaira.com/kagaku_86.html

    • Related Report
      2013 Final Research Report
  • [Journal Article] Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate under both Microgravity and Hypergravity induced by Parabolic Flight.2012

    • Author(s)
      Bai Y
    • Journal Title

      J Pharmacol Sci.

      Volume: 119 Pages: 381-389

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibition of Phosphodiesterase Type 3 Dilates the Rat Ductus Arteriosus without Inducing Intimal Thickening2012

    • Author(s)
      Ichikawa Y
    • Journal Title

      Circ J

      Volume: 76 Pages: 2456-2464

    • NAID

      10030875150

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Low-dose Thromboxane A2 Receptor Stimulation Promotes Closure of the Rat Ductus Arteriosus with Minimal Adverse Effects2012

    • Author(s)
      Yokota T
    • Journal Title

      Pediatr Res

      Volume: 72 Pages: 129-136

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] 三次元血管モデルを用いた動脈硬化性疾患の機序解明 Elucidation of Molecular Mechanisms of Atherosclerosis by Three-Dimensional (3D)-Layered Blood Vessel Constructs2012

    • Author(s)
      横山 詩子
    • Journal Title

      科学と工業

      Volume: 86 Pages: 21-27

    • Related Report
      2012 Research-status Report
  • [Presentation] 血管弾性線維形成の機序解明に向けた三次元血管壁組織の開発2013

    • Author(s)
      横山詩子
    • Organizer
      第2回三次元生体組織構築公開シンポジウム-世界基準へのチャレンジ-
    • Place of Presentation
      東京
    • Year and Date
      2013-11-28
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] プロスタグランディンEによる血管弾性線維の制御メカニズムと新たな三次元血管モデルの可能性2013

    • Author(s)
      横山詩子
    • Organizer
      第18回NCVC研究者交流会
    • Place of Presentation
      大阪(国立循環器病研究所セミナー)
    • Year and Date
      2013-09-27
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular mechanisms of the regulation of vascular elastic fiber formation and development of a new 3D vascular model2013

    • Author(s)
      Yokoyama U
    • Organizer
      The 36^<th> Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      Kobe
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Molecular Mechanisms of Dynamic Cardiovascular Adaptation from Fetal to Neonatal Life2013

    • Author(s)
      Yokoyama U
    • Organizer
      The 90^<th> Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Proteomic analysis identified prostaglandin E2-induced proteins in tissues from patients with aortic aneurysm2013

    • Author(s)
      Ishiwata R, Yokoyama U, Arakawa N, Nomura A, Oshima T, Minamisawa S, Ishikawa Y
    • Organizer
      The 90^<th> Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Final Research Report
  • [Presentation] Molecular mechanisms of the regulation of vascular elastic fiber formation and development of a new 3D vascular model2013

    • Author(s)
      Yokoyama U
    • Organizer
      The 36th Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 血管弾性線維形成の機序解明に向けた三次元血管壁組織の開発2013

    • Author(s)
      横山詩子
    • Organizer
      第2回三次元生体組織構築公開シンポジウム
    • Place of Presentation
      化学会館ホール(東京都千代田区)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] プロスタグランディンEによる血管弾性線維の制御メカニズムと新たな三次元血管モデルの可能性2013

    • Author(s)
      横山詩子
    • Organizer
      国立循環器病研究所セミナー、第18 回NCVC 研究者交流会
    • Place of Presentation
      国立循環器病研究所(大阪府吹田市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Molecular Mechanisms of Dynamic Cardiovascular Adaptation from Fetal to Neonatal Life2013

    • Author(s)
      Yokoyama U
    • Organizer
      The 90th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      タワーホール船堀(東京都)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Proteomic analysis of aortic aneurysm2013

    • Author(s)
      Ishiwata R
    • Organizer
      The 90th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      タワーホール船堀(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] 動脈硬化性疾患の機序解明にむけた三次元血管モデルの開発2012

    • Author(s)
      横山詩子
    • Organizer
      三次元生体組織構築公開シンポジウム-世界基準へのチャレンジ-
    • Place of Presentation
      東京
    • Year and Date
      2012-11-28
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] プロスタグランジンEシグナルと弾性線維形成―動脈管閉鎖や大動脈瘤形成への関与2012

    • Author(s)
      横山詩子
    • Organizer
      医学研究の基礎を語り合う集いTokyo Heart Development Club
    • Place of Presentation
      東京
    • Year and Date
      2012-06-25
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] Rat Smooth Muscle Cells within Three Dimensional Cellular Multilayers Exhibit Contractile Phenotypes and Layered Elastic Fiber2012

    • Author(s)
      Ishiwata R, Yokoyama U, Kadowaki K, Matsusaki M, Akashi M, Ishikawa Y, Minamisawa S
    • Organizer
      The 8^<th> Congress of Asian Society for Pediatric Research
    • Place of Presentation
      Seoul, Korea
    • Related Report
      2013 Final Research Report
  • [Presentation] Rat Smooth Muscle Cells within Three Dimensional Cellular Multilayers Exhibit Contractile Phenotypes and Layered Elastic Fiber2012

    • Author(s)
      Ishiwata R
    • Organizer
      The 8th Congress of Asian Society for Pediatric Research
    • Place of Presentation
      Seoul(Korea)
    • Related Report
      2012 Research-status Report
  • [Presentation] 動脈硬化性疾患の機序解明にむけた三次元血管モデルの開発

    • Author(s)
      横山 詩子
    • Organizer
      三次元生体組織構築公開シンポジウムー世界基準へのチャレンジー
    • Place of Presentation
      化学会館(東京都)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] プロスタグランジンE シグナルと弾性線維形成―動脈管閉鎖や大動脈瘤形成への関与

    • Author(s)
      横山 詩子
    • Organizer
      医学研究の基礎を語り合う集いTokyo Heart Development Club
    • Place of Presentation
      東京慈恵医科大学(東京都)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Book] Nanomedicine and Nanotoxicology2014

    • Author(s)
      Yokoyama U, Ishikawa Y
    • Total Pages
      8
    • Publisher
      Springer
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Book] Congenital Heart Disease - Selected Aspects2012

    • Author(s)
      Minamisawa S, Yokoyama U
    • Total Pages
      348
    • Publisher
      InTech
    • Related Report
      2013 Final Research Report
  • [Book] InTech2012

    • Author(s)
      Minamisawa S
    • Total Pages
      348
    • Publisher
      Congenital Heart Disease - Selected Aspects
    • Related Report
      2012 Research-status Report
  • [Remarks] ホームページ:横浜市立大学医学部循環制御医学

    • URL

      http://www-user.yokohama-cu.ac.jp/~seiri1

    • Related Report
      2013 Final Research Report
  • [Remarks] 横浜市立大学医学部循環制御医学

    • URL

      http://www-user.yokohama-cu.ac.jp/~seiri1/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 横浜市立大学医学部循環制御医学ホームページ

    • URL

      http://www-user.yokohama-cu.ac.jp/~seiri1/

    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 三次元組織体及びその製造方法2013

    • Inventor(s)
      明石満、松崎典弥、石川義弘、横山詩子
    • Industrial Property Rights Holder
      明石満、松崎典弥、石川義弘、横山詩子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-10-10
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 三次元組織体及びその製造方法2013

    • Inventor(s)
      明石満、松崎典弥、石川義弘、横山詩子
    • Industrial Property Rights Holder
      明石満、松崎典弥、石川義弘、横山詩子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-10-10
    • Related Report
      2013 Annual Research Report

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

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